Pathogens

16 pages, 7144 KB

Open AccessEditor’s ChoiceArticle

The Association of Macavirus and Ovine Gammaherpesvirus 2 with Pneumonia in Beef Cattle from Mato Grosso, Brazil

by Julia Raisa Ximenes Figueiredo, Flavia Helena Pereira Silva, Juliana Torres Tomazi Fritzen, Beatriz Martins Machado, Fernanda Pinto Ferreira, Karina Rodrigues Gomes Ferreira, Sébastien Buczinski, Amauri Alcindo Alfieri and Selwyn Arlington Headley

Pathogens 2025, 14(9), 945; https://doi.org/10.3390/pathogens14090945 - 18 Sep 2025

Cited by 1 | Viewed by 830

Abstract

This study investigated the possible occurrence of pulmonary disease in beef cattle from 13 municipalities within the State of Mato Grosso (MT), Brazil. The state of MT is a leading player in beef cattle production in Brazil, but with comparatively few data relative [...] Read more.

This study investigated the possible occurrence of pulmonary disease in beef cattle from 13 municipalities within the State of Mato Grosso (MT), Brazil. The state of MT is a leading player in beef cattle production in Brazil, but with comparatively few data relative to the occurrence of pulmonary disease or ovine gammaherpesvirus 2 (OvGHV2)-related infections in cattle. Pulmonary samples from 44 beef cattle, with ages ranging between 18 and 28 months, were collected during slaughter and processed to determine the patterns of pulmonary lesions. Additionally, duplicate fragments were used in immunohistochemical (IHC) assays designed to detect malignant catarrhal fever (MCFV) antigens and in molecular assays to amplify 10 agents associated with the development of bovine respiratory disease (BRD). Interstitial pneumonia (IP) was diagnosed in most of the lungs (98%; 43/44) evaluated from all municipalities. MCFV antigens were detected in 37% (16/43) of the animals with IP. Only four pathogens were amplified by molecular assays within the lungs of cattle with IP: OvGHV2 (23%; 10/43), bovine viral diarrhea virus (12%; 5/43), bovine coronavirus (7%; 3/43), and Mannheimia haemolytica (2%; 1/43). The nucleic acids of bovine respiratory syncytial virus, bovine alphaherpesvirus 1, bovine parainfluenza virus 3, Pasteurella multocida, Histophilus somni, and Mycoplasmopsis (Mycoplasma) bovis were not amplified. Singular infections in cattle from municipalities were associated with MCFV (n = 3) and OvGHV2 (n = 2), while OvGHV2 occurred in all dual and triple infections. However, in four animals with IP, none of the disease pathogens identified were detected. Statistically, MCFV antigens were more frequently (p = 0.048) detected in the lungs of female (75%; 12/16) cattle with IP relative to males (25%; 4/16). Additionally, there was a positive correlation (p < 0.001) between the IHC detection of MCFV antigens within the bronchial epithelium and the epithelium of peribronchial glands of cattle with IP. This is the first study to statistically demonstrate that female cattle are at greater risk of developing MCFV-related infections as compared to male animals. The detection of OvGHV2 in singular and multiple infections during this investigation supports earlier studies that associate this pathogen with the development of pulmonary disease in cattle, indicating that OvGHV2 can contribute to the etiology of IP. Additionally, the detection of OvGHV2-induced infections in asymptomatic cattle suggests that all animals were subclinically infected, confirming that subclinically OvGHV2-induced infections may be widespread in ruminants from Brazil. Furthermore, the occurrence of atypical interstitial pneumonia cannot be discarded, particularly in animals with IP but without any associated pathogen. These initial findings suggest the need for a more elaborate investigation to understand the dynamics of pulmonary disease within this state. Full article

(This article belongs to the Section Viral Pathogens)

► Show Figures

Figure 1

27 pages, 3758 KB

Open AccessEditor’s ChoiceArticle

Exploring the Virome of Nile Tilapia (Oreochromis niloticus) Using Metagenomic Analysis

by Amira Ezzat, Ahmed Abd El Wahed, Arianna Ceruti, Amel M. El Asely, Mohamed Shawky Khalifa, Andrew D. Winters, Uwe Truyen, Adel A. Shaheen and Mohamed Faisal

Pathogens 2025, 14(9), 935; https://doi.org/10.3390/pathogens14090935 - 16 Sep 2025

Cited by 2 | Viewed by 1630

Abstract

Nile tilapia (Oreochromis niloticus) is an indispensable source of high-quality protein worldwide. Along with the exponential expansion of tilapia aquaculture, several novel pathogenic viruses have emerged, and some cause significant economic losses. Unfortunately, there is scarce information on the biology and [...] Read more.

Nile tilapia (Oreochromis niloticus) is an indispensable source of high-quality protein worldwide. Along with the exponential expansion of tilapia aquaculture, several novel pathogenic viruses have emerged, and some cause significant economic losses. Unfortunately, there is scarce information on the biology and epidemiology of these viruses. This exploratory metagenomic study used Oxford Nanopore Technology (ONT) sequencing to profile the virome compositions of both wild and farmed Nile tilapia across five regions in Egypt. The Nile tilapia virome was dominated by two double-stranded DNA bacteriophages, Muvirus mu and M. sfmu, which constituted 79.8% of the detected sequences. Eukaryotic viruses, including members of the families Amnoonviridae, Peribunyaviridae, and Baculoviridae, were also identified. Two giant DNA viruses known to infect Acanthamoeba spp., Mollivirus sp., and Pandoravirus sp. were identified in the spleen virome of tilapia from a single sampling site. The diversity analysis showed no significant differences among tissue types or sampling sites. Phylogenetic analyses were performed on a single virus detected of potential pathogenicity, an amnoonvirus. The analyses demonstrated that the detected virus is a member of the family Amnoonviridae and placed it alongside members of the Tilapinevirus genus. The virus, however, was distinct from the other two members in the genus: T. tilapae and T. poikilos. This study underscores the usefulness of ONT in providing a foundational understanding of the Nile tilapia virome. Full article

(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)

► Show Figures

Figure 1

35 pages, 3316 KB

Open AccessEditor’s ChoiceReview

Silent Carriers: The Role of Rodents in the Emergence of Zoonotic Bacterial Threats

by Shereen Basiouni, Alfonso J. Rodriguez-Morales, Awad A. Shehata and Phelipe Magalhães Duarte

Pathogens 2025, 14(9), 928; https://doi.org/10.3390/pathogens14090928 - 15 Sep 2025

Cited by 1 | Viewed by 2782

Abstract

Rodents are recognized as significant reservoirs for a broad range of zoonotic pathogens, including bacteria, viruses, and parasites, many of which have substantial implications for human and animal health. The intensifying interaction between humans and rodent populations, fuelled by urbanization, climate change, and [...] Read more.

Rodents are recognized as significant reservoirs for a broad range of zoonotic pathogens, including bacteria, viruses, and parasites, many of which have substantial implications for human and animal health. The intensifying interaction between humans and rodent populations, fuelled by urbanization, climate change, and global trade, has amplified the risk of zoonotic disease transmission. This review compiles and examines current knowledge on key rodent-borne bacterial diseases, including leptospirosis, rat-bite fever, plague, salmonellosis, tularemia, Lyme disease, rickettsioses, Babesiosis, and associated parasitic infections such as toxoplasmosis and Chagas disease. Each disease is analyzed in terms of its etiology, transmission, clinical manifestations, diagnostic tools, and treatment options, with a particular focus on the impact of environmental changes. Emphasizing a One Health perspective, this work highlights the importance of interdisciplinary approaches to the surveillance, prevention, and control of rodent-borne zoonoses, particularly in the context of increasing climate variability and anthropogenic pressures. Full article

(This article belongs to the Special Issue New Insights into Zoonotic Intracellular Pathogens)

► Show Figures

Figure 1

17 pages, 606 KB

Open AccessEditor’s ChoiceReview

H5N1 Clade 2.3.4.4b: Evolution, Global Spread, and Host Range Expansion

by Klaudia Chrzastek, Carolin M. Lieber and Richard K. Plemper

Pathogens 2025, 14(9), 929; https://doi.org/10.3390/pathogens14090929 - 15 Sep 2025

Cited by 3 | Viewed by 3656

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype pose a continuous threat to animal and public health due to their zoonotic potential, rapid evolution, and ability to spread across continents. Since the emergence of the A/goose/Guangdong/1/96 (GsGD) H5 lineage in 1996, [...] Read more.

Highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype pose a continuous threat to animal and public health due to their zoonotic potential, rapid evolution, and ability to spread across continents. Since the emergence of the A/goose/Guangdong/1/96 (GsGD) H5 lineage in 1996, several clades have caused devastating outbreaks in poultry and wild bird populations, occasionally resulting in human infections. Of the many clades that have evolved, only three—clades 2.2, 2.3.2.1, and most recently 2.3.4.4b—have demonstrated the ability to spread globally. The 2.3.4.4b clade has raised significant concern due to its continuous geographic expansion, establishment in new ecosystems, including Antarctica, and increasing reports of mammalian infections, including companion animals, marine mammals, and livestock. Recently, cow-to-cow and cow-to-human transmission marked a paradigm shift in the epidemiology of avian influenza and emphasized the need for continued surveillance. This review summarizes the historical emergence, global spread, and molecular evolution of H5 HPAIVs with a specific focus on the recent expansion of clade 2.3.4.4b and its capacity for mammalian spillover. Full article

(This article belongs to the Special Issue Emerging and Re-Emerging Avian Influenza Viruses in Wildlife)

► Show Figures

Figure 1

16 pages, 3894 KB

Open AccessEditor’s ChoiceArticle

Trends in Antibiotic Resistance of Escherichia coli Strains Isolated from Clinical Samples (2019–2023): A Hospital-Based Retrospective Analysis

by Claudia Daniela Goleanu (Vasiloiu), Corneliu Ovidiu Vrancianu, Daria Adelina Goleanu, Monica Marilena Tantu and Ortansa Csutak

Pathogens 2025, 14(9), 927; https://doi.org/10.3390/pathogens14090927 - 13 Sep 2025

Cited by 4 | Viewed by 4294

Abstract

Background: Antimicrobial resistance (AMR) is a major public health concern. Urinary tract infections (UTIs) account for up to 85–90% of community-acquired cases. The COVID-19 pandemic disrupted healthcare access and may have influenced resistance patterns. In this context, we retrospectively evaluated the antibiotic resistance [...] Read more.

Background: Antimicrobial resistance (AMR) is a major public health concern. Urinary tract infections (UTIs) account for up to 85–90% of community-acquired cases. The COVID-19 pandemic disrupted healthcare access and may have influenced resistance patterns. In this context, we retrospectively evaluated the antibiotic resistance dynamics of various bacterial strains isolated between 2019 and 2023 in a hospital unit; Methods: A total of 8217 clinical specimens (urine, wound secretions, sputum, pharyngeal exudate, nasal exudate, tracheal secretions, vaginal and cervical secretions, puncture fluids, purulent secretions, blood, ear secretions, eye secretions) were processed using standard microbiological techniques. Pathogen identification and susceptibility testing were performed with the VITEK 2 Compact system, following CLSI guidelines. Results: Following the analysis of 8217 clinical samples collected over a five-year period (2019–2023), a total of 2900 microorganisms were isolated and identified. Among these, the most frequently encountered were E. coli strains, with 1204 isolates. Urine cultures represented 71.3% of all processed samples. Out of these 5860 urine cultures, 1530 (26%) were positive. The resistance of E. coli strains to ampicillin (48–55.2%), trimethoprim/sulfamethoxazole (22.9–34%), and ciprofloxacin (21.4–31.5%) remained high throughout the period. ESBL-producing strains peaked at 17.6% in 2020, with multidrug resistance rates ranging from 14% to 22.4%. Conclusions: E. coli strains displayed persistently high resistance to ampicillin, trimethoprim/sulfamethoxazole, and ciprofloxacin, with peaks in ESBL production and multidrug resistance during the COVID-19 pandemic. These trends underscore the importance of continuous surveillance and antibiotic stewardship, with direct implications for empirical UTI therapy and broader strategies to mitigate the public health impact of antimicrobial resistance. Full article

► Show Figures

Figure 1

14 pages, 1481 KB

Open AccessEditor’s ChoiceArticle

E2 Tyrosine 102 Regulates MmuPV1 Pathogenesis In Vivo

by Jessica Gonzalez, Marsha DeSmet, Kennedy Stoll, Leny Jose, Neil Christensen and Elliot J. Androphy

Pathogens 2025, 14(9), 913; https://doi.org/10.3390/pathogens14090913 - 11 Sep 2025

Viewed by 745

Abstract

The papillomavirus (PV) life cycle is strictly controlled and can be divided into the following three distinct stages: initial infection, maintenance, and amplification. The papillomavirus E2 gene encodes a multifunctional protein responsible for regulating transcription and replication by recruiting viral and host factors [...] Read more.

The papillomavirus (PV) life cycle is strictly controlled and can be divided into the following three distinct stages: initial infection, maintenance, and amplification. The papillomavirus E2 gene encodes a multifunctional protein responsible for regulating transcription and replication by recruiting viral and host factors to the viral DNA genome. Our lab has previously reported that tyrosine 102 may impact bovine (BPV) and human (HPV) viral replication in cell culture systems. This tyrosine is conserved in the E2 protein of the murine papillomavirus MmuPV1. To investigate how this amino acid impacts the MmuPV1 lifecycle in vivo, we generated potential phosphorylation mimetic (Y102E) and phosphorylation deficient (Y102F) mutants in the E2 open reading frame. The Y102F mutant protein supported both transcriptional activation and transient replication, while Y102E was defective. However, Y102E was capable of associating with E1 and the Brd4 C-terminal motif. When these E2-mutated MmuPV1 genomes were introduced into the skin of immunocompromised mice, only Y102F was capable of inducing papilloma development and production of infectious progeny virus. These findings demonstrate that while highly conserved, tyrosine at this position is not required by the virus. These data suggest that the chemical nature of the amino acid at this position can influence E2 activity and viral replication. Full article

(This article belongs to the Section Viral Pathogens)

► Show Figures

Figure 1

20 pages, 4590 KB

Open AccessEditor’s ChoiceArticle

Immunization with mRNA-LNPs Encoding Ornithodoros Argasid Tick Antigens Induces Humoral Immune Responses and Tick Resistance

by Ana Oleaga, Ana Laura Cano-Argüelles, María González-Sánchez, Rocío Vizcaíno-Marín and Ricardo Pérez-Sánchez

Pathogens 2025, 14(9), 914; https://doi.org/10.3390/pathogens14090914 - 11 Sep 2025

Viewed by 1013

Abstract

Argasid ticks Ornithodoros erraticus and Ornithodoros moubata are major vectors of zoonotic pathogens, including the African swine fever virus and relapsing fever Borrelia spp., and their control is essential to reduce disease transmission. In this study, we evaluated the immunogenicity and protective efficacy [...] Read more.

Argasid ticks Ornithodoros erraticus and Ornithodoros moubata are major vectors of zoonotic pathogens, including the African swine fever virus and relapsing fever Borrelia spp., and their control is essential to reduce disease transmission. In this study, we evaluated the immunogenicity and protective efficacy of four Ornithodoros tick antigens formulated as mRNA–lipid nanoparticles (mRNA-LNPs): OeSOD, OeTSP1, OmPLA2, and Om86. Rabbits were immunised with three doses of each mRNA-LNP construct, and immune responses and tick biological parameters were assessed following infestation with both tick species. All mRNA-LNP constructs induced antigen-specific IgG responses that recognised native proteins in tick saliva and midgut extracts. Vaccination resulted in significant reductions in female oviposition and fertility, which correlated with antibody levels, and yielded protective efficacies of 21.9–41.6% against O. moubata and 23.1–41.6% against O. erraticus. Notably, the mRNA-LNPs of OeSOD and OeTSP1 outperformed their recombinant counterparts against O. moubata, and Om86 mRNA-LNP conferred markedly improved protection against both O. moubata and O. erraticus. These findings highlight the potential of mRNA-LNP vaccines to induce effective anti-argasid tick immunity and provide a promising platform for the development of sustainable strategies to control argasid ticks and associated pathogens. Full article

(This article belongs to the Section Ticks)

► Show Figures

Graphical abstract

20 pages, 1324 KB

Open AccessEditor’s ChoiceReview

Mycobacterium marinum Immune Evasion in Zebrafish

by Priyank Kumar, Joshua Cameron, Beatrice Saviola and Vishwanath Venketaraman

Pathogens 2025, 14(9), 908; https://doi.org/10.3390/pathogens14090908 - 10 Sep 2025

Cited by 1 | Viewed by 2077

Abstract

Fish mycobacteriosis, a chronic progressive disease caused by nontuberculous mycobacteria (NTM), affects marine, brackish, and freshwater fish. Mycobacterium marinum (M. marinum), the most important of the NTM, infects fresh and marine water fish causing necrotizing granulomas and associated morbidity and mortality. [...] Read more.

Fish mycobacteriosis, a chronic progressive disease caused by nontuberculous mycobacteria (NTM), affects marine, brackish, and freshwater fish. Mycobacterium marinum (M. marinum), the most important of the NTM, infects fresh and marine water fish causing necrotizing granulomas and associated morbidity and mortality. M. marinum causes disease in zebrafish in a dose-dependent fashion. The M. marinum-induced disease in the zebrafish is associated with the development of necrotizing granulomas with abundant bacteria in the necrotic areas. Acute infection with high infectious doses of M. marinum infection in zebrafish was characterized by uncontrolled replication of the pathogen and death of all fish within 16 days, while chronic infections were marked by the formation of granulomas in different organs and longer survival in the range of 4–8 weeks. This review therefore synthesizes recent advances in our understanding of M. marinum’s infection of zebrafish, molecular pathogenesis, virulence mechanisms, and immune evasion strategies in zebrafish, while also highlighting the host immune effector responses and the virulence mechanisms of M. marinum. Full article

(This article belongs to the Special Issue Infectious Diseases in Aquatic Animals)

► Show Figures

Figure 1

25 pages, 1146 KB

Open AccessEditor’s ChoiceReview

Emerging Challenges in Salmonella Control: The Need for Innovative and Sustainable Disinfection Strategies in Poultry Farming

by Nicla Gentile, Laura Lorenzo-Rebenaque, Ana Marco-Fuertes, Laura Montoro-Dasi and Clara Marin

Pathogens 2025, 14(9), 912; https://doi.org/10.3390/pathogens14090912 - 10 Sep 2025

Cited by 3 | Viewed by 2698

Abstract

Salmonella is one of the primary causes of foodborne infections worldwide and is often linked to the consumption of poultry products. Despite the implementation of numerous control programmes, the persistence of Salmonella in poultry environments remains a challenge, exacerbated by the emergence of [...] Read more.

Salmonella is one of the primary causes of foodborne infections worldwide and is often linked to the consumption of poultry products. Despite the implementation of numerous control programmes, the persistence of Salmonella in poultry environments remains a challenge, exacerbated by the emergence of strains resistant to traditional disinfectants. This review examines the key factors associated with the limitations of disinfection and the new strategies employed in poultry production, underscoring the need for more sustainable and effective alternative solutions. Various chemical (nanoparticles), physical (ultraviolet light, heat, pressurised steam, infrared radiation) and biological (bacteriophages, essential oils, and positive biofilm) treatments are examined. Of the various alternatives assessed, some have shown promising antimicrobial activity against Salmonella in vitro and under experimental conditions. However, their application in real-field settings is still limited, and few studies evaluate their effectiveness on a commercial scale. The review emphasises the importance of integrating these alternatives within broader biosecurity programmes, supported by clear regulations to minimise the risk of transmission. In conclusion, the adoption of innovative and sustainable approaches, combined with strengthened biosecurity measures, represents a key strategy to reduce Salmonella contamination in poultry farms, protect public health and promote responsible production systems. Full article

(This article belongs to the Special Issue Salmonella: A Global Health Threat and Food Safety Challenge)

► Show Figures

Figure 1

22 pages, 1590 KB

Open AccessEditor’s ChoiceReview

Bacterial Puppeteering: How the Stealth Bacterium Coxiella Pulls the Cellular Strings

by Dylan Ruart, Juliette Riedinger, Sihem Zitouni, Arthur Bienvenu, Matteo Bonazzi and Eric Martinez

Pathogens 2025, 14(9), 896; https://doi.org/10.3390/pathogens14090896 - 5 Sep 2025

Cited by 1 | Viewed by 1166

Abstract

Coxiella burnetii, the causative agent of Q fever, is a highly infectious pathogen capable of invading diverse cell types, from alveolar macrophages to trophoblasts. Within host cells, it establishes a replicative niche named Coxiella-containing vacuole (CCV). This is driven by effector [...] Read more.

Coxiella burnetii, the causative agent of Q fever, is a highly infectious pathogen capable of invading diverse cell types, from alveolar macrophages to trophoblasts. Within host cells, it establishes a replicative niche named Coxiella-containing vacuole (CCV). This is driven by effector proteins secreted by the bacterium into the host cell cytoplasm via a Type 4b Secretion System (T4SS). Advances in axenic culture and mutagenesis allowed the characterization of Coxiella effector proteins, revealing their host targets and strategies of cellular subversion. This review highlights recent insights into Coxiella effector proteins and their manipulation of host processes, from vesicular trafficking to innate immunity. Full article

(This article belongs to the Special Issue Coxiella burnetii: The Host Immune Response, Host–Pathogen Interaction and Pathogenesis)

► Show Figures

Figure 1

11 pages, 707 KB

Open AccessEditor’s ChoiceArticle

Influenza D Virus Circulation Among Bovines, Swine, Equines, and Wild Boars in Italy: A Sero-Epidemiological Study

by Alessandro Falsini, Chiara Coppola, Aurora Fiori, Domenico Buonavoglia, Serena Marchi, Emanuele Montomoli, Francesco Pellegrini, Gianvito Lanave, Vito Martella, Michele Camero and Claudia Maria Trombetta

Pathogens 2025, 14(9), 891; https://doi.org/10.3390/pathogens14090891 - 5 Sep 2025

Cited by 3 | Viewed by 1175

Abstract

Influenza D virus (IDV), belonging to the Orthomyxoviridae family, was first discovered in 2011 in pigs. Surveys in humans and animals have been carried out to decipher IDV ecology. In this seroepidemiological study, we investigated the circulation of IDV lineages across Italy in [...] Read more.

Influenza D virus (IDV), belonging to the Orthomyxoviridae family, was first discovered in 2011 in pigs. Surveys in humans and animals have been carried out to decipher IDV ecology. In this seroepidemiological study, we investigated the circulation of IDV lineages across Italy in livestock and wildlife animals. A total of 1038 animal serum samples (from 246 bovines, 249 swine, 98 equines, and 445 wild boars) were tested using hemagglutination inhibition and virus neutralization assays. The results confirm bovines as the primary reservoir for IDV, with high seroprevalence for both D/660 (87%) and D/OK (80%) strains. Swine and equines demonstrated limited exposure, suggesting they are infrequent spillover hosts. Notably, wild boars showed high seroprevalence, especially for the D/660 lineage (80%), indicating their potential role in a wildlife transmission cycle. Continuous surveillance in both livestock and wildlife is essential to monitor the spread and evolution of IDV. Full article

(This article belongs to the Special Issue Current Challenges in Veterinary Virology)

► Show Figures

Figure 1

14 pages, 2079 KB

Open AccessEditor’s ChoiceArticle

γδ T Cells Mediate Protective Immunity Following Vaccination with an Insect-Based Chikungunya Fever Vaccine in Mice

by Leslie Rodriguez, Awadalkareem Adam, Huanle Luo, Samantha R. Osman, Kenneth Plante, Shannan L. Rossi, Scott C. Weaver and Tian Wang

Pathogens 2025, 14(9), 863; https://doi.org/10.3390/pathogens14090863 - 30 Aug 2025

Viewed by 1852

Abstract

Eilat (EILV)/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human [...] Read more.

Eilat (EILV)/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human primates. The underlying immune mechanism of the vaccine-induced host protection remains unknown. γδ T cells react to WT CHIKV infection by controlling the virus-induced tissue inflammation and damage. Here, we found that γδ T cells contribute to EILV/CHIKV-induced host protection against WT CHIKV infection. TCRδ^−/− mice, which are deficient of γδ T cells, had impaired CHIKV-specific CD8⁺ T cell responses, antibody production and memory B cell responses following vaccination. Both antibody and CD8⁺ T cells of EILV/CHIKV-vaccinated mice were required for protection type I interferon receptor deficient mice from lethal WT CHIKV infection. Moreover, γδ T cells expanded quickly in response to EILV/CHIKV vaccination. TCRδ^−/− mice, had lower levels of innate immune cytokines and impaired activation of antigen presenting cell (APCs). Overall, γδ T cells contribute to EILV/CHIKV-induced host protection by promoting APC maturation, T cell priming and the induction of humoral immune responses upon EILV/CHIKV vaccination. Full article

(This article belongs to the Special Issue Infectious Diseases and Tropical Infections: Epidemiology, Transmission, Treatment, and Prevention)

► Show Figures

Figure 1

18 pages, 3488 KB

Open AccessEditor’s ChoiceArticle

Whole Genome Characterization of Leptospira kirschneri Serogroup Pomona in Croatia: Insights into Its Diversity and Evolutionary Emergence

by Iva Benvin, Taylor K. Paisie, Ines Caetano Varanda, Zachary P. Weiner, Robyn A. Stoddard, Jay E. Gee, Christopher A. Gulvik, Chung K. Marston, Vesna Mojčec Perko, Zrinka Štritof, Josipa Habuš, Josip Margaletić, Marko Vucelja, Linda Bjedov and Nenad Turk

Pathogens 2025, 14(9), 860; https://doi.org/10.3390/pathogens14090860 - 29 Aug 2025

Cited by 2 | Viewed by 1501

Abstract

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira spp. with small rodents serving as the main reservoir. In Croatia, the serogroup Pomona has been detected most frequently, but its genomic diversity remains insufficiently characterized. This study presents the first whole genome sequencing [...] Read more.

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira spp. with small rodents serving as the main reservoir. In Croatia, the serogroup Pomona has been detected most frequently, but its genomic diversity remains insufficiently characterized. This study presents the first whole genome sequencing analysis of 48 Croatian Leptospira spp. isolates collected from small rodents over a 14-year period. Serological typing confirmed that all the isolates belonged to the serogroup Pomona. Genomic analysis assigned them to L. kirschneri based on high genomic similarity using average nucleotide identity (ANI). The isolates were assigned to ST-98 using traditional multilocus sequence typing (MLST), while cgMLST identified seven genotype clusters, many of which showed geographic structuring. Phylogenetic analyses based on single nucleotide polymorphisms (SNPs) supported this structure and revealed a monophyletic clade of Croatian isolates distinct from other global L. kirschneri strains. Serological typing, MLST, and phylogenetic clustering support classification of the isolates as L. kirschneri, serogroup Pomona, most likely serovar Mozdok, although serovar Tsaratsovo cannot be excluded. These results indicate the existence of a geographically restricted and potentially host-adapted lineage of L. kirschneri in Croatia. The integration of ecological, serological, and genomic data in this study emphasizes the value of whole genome sequencing for understanding the population biology of Leptospira spp. serogroup Pomona. Moreover, it supports targeted, country-specific surveillance and control strategies for leptospirosis through the identification of circulating serovars and species in reservoir hosts, in line with a One Health approach. Full article

► Show Figures

Figure 1

20 pages, 1010 KB

Open AccessEditor’s ChoiceArticle

Emergence of Carbapenem-Resistant Klebsiella pneumoniae in a Romanian Infectious Diseases Hospital

by Dragos Stefan Lazar, Maria Nica, Corina Oprisan, Maricela Vlasie, Ilie-Andrei Condurache, Simin Aysel Florescu and George Sebastian Gherlan

Pathogens 2025, 14(9), 859; https://doi.org/10.3390/pathogens14090859 - 29 Aug 2025

Cited by 1 | Viewed by 2625

Abstract

Klebsiella pneumoniae, a member of the Enterobacterales Order, often colonises the gut and causes diverse infections, including bloodstream, urinary, and respiratory infections. The rise in carbapenem-resistant sFtrains, especially those producing enzymes like K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Oxacillinase 48 [...] Read more.

Klebsiella pneumoniae, a member of the Enterobacterales Order, often colonises the gut and causes diverse infections, including bloodstream, urinary, and respiratory infections. The rise in carbapenem-resistant sFtrains, especially those producing enzymes like K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Oxacillinase 48 (OXA48), or combinations (NDM+OXA48-like), poses a significant threat across Europe, notably in Romania. These strains spread rapidly via mobile genetic elements, complicating treatment. Methods: A retrospective study of multidrug-resistant (MDR) K. pneumoniae strains isolated from clinical samples collected at an infectious diseases hospital in Romania. Results: We analysed the evolution of carbapenemases and their combinations from 2010 to 2024, with the rising antibiotic consumption, particularly during the COVID-19 pandemic. The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) rose from 4.9% in 2010 to 41.6% in 2024. There was an overall antibiotic use increase, especially colistin (186%) between 2019–2024. Additionally, we examined the dynamics of antibiotic susceptibility that decreased in 2023–2024 and found that susceptibility of NDM+OXA48-like isolates to colistin was 16.5% and to cefiderocol 58.5%. Conclusions: The rising prevalence of K. pneumoniae strains with complex resistance mechanisms, coupled with a significant reduction in available treatment options, demands a fundamental paradigm shift in the management of these infections. Full article

(This article belongs to the Section Bacterial Pathogens)

► Show Figures

Figure 1

25 pages, 690 KB

Open AccessEditor’s ChoiceReview

Chemical Treatments Tested Against Xylella fastidiosa: Strategies, Successes and Limitations

by Letizia Portaccio, Marzia Vergine, Alessandro Bene, Mariarosaria De Pascali, Erika Sabella, Luigi De Bellis and Andrea Luvisi

Pathogens 2025, 14(9), 840; https://doi.org/10.3390/pathogens14090840 - 23 Aug 2025

Cited by 2 | Viewed by 2627

Abstract

Xylella fastidiosa (Xf) is a Gram-negative bacterium responsible for severe diseases in several commercially significant crops, including olive, grapevine, citrus and almond. Its management is particularly challenging due to its transmission via widespread vector insects, its ability to form biofilms, its [...] Read more.

Xylella fastidiosa (Xf) is a Gram-negative bacterium responsible for severe diseases in several commercially significant crops, including olive, grapevine, citrus and almond. Its management is particularly challenging due to its transmission via widespread vector insects, its ability to form biofilms, its high genetic diversity and, sometimes, latent symptoms. Current control strategies focus on integrated and preventive approaches, including the use of resistant varieties, agronomic practices, and vector control through chemical and biological methods. Direct control of the bacterium has always been a complex challenge that includes strategies to limit vector presence and activity in the field; however, several compounds have recently been evaluated that are able to inhibit biofilm formation and Xf growth. This review provides an up-to-date summary of studies investigating the efficacy of various treatments based on organic compounds, synthetic molecules and salt- or metal-based formulations. By evaluating the results of in vitro and in vivo experiments, the most promising solutions were identified that address the main challenges and limitations of chemical control strategies. These include N-acetylcysteine and zinc- and copper-based formulations, which are effective and potentially transferable to the field for crops such as citrus and olive trees. Antimicrobial peptides and nanoparticles, on the other hand, have demonstrated high efficacy in vitro, although further studies directly in the field are required. The evidence emerging from the analyzed studies offer insights to guide future research towards more effective and sustainable management approaches to mitigate the spread and impact of Xf. Full article

(This article belongs to the Section Bacterial Pathogens)

► Show Figures

Figure 1

10 pages, 851 KB

Open AccessEditor’s ChoiceArticle

Introduction and Spatial–Temporal Distribution of Oropouche Virus in Rio de Janeiro State, Brazil

by Fábio Burack da Costa, Andrea Cony Cavalcanti, Rafael Santos Erbisti, Vanessa Zaquieu Dias, Cristiane Gomes de Castro Moreira, Mateus Marques Grifo, Maria Carmelita dos Santos Vaz, Adriana Cardoso Camargo, Leandro Magalhães de Souza, Flávia Barreto dos Santos, Mário Sérgio Ribeiro, Viviana Malirat, Nildimar Alves Honório and Renata Campos Azevedo

Pathogens 2025, 14(8), 833; https://doi.org/10.3390/pathogens14080833 - 21 Aug 2025

Cited by 3 | Viewed by 1587

Abstract

The Oropouche virus (OROV) has been circulating in the Amazon region since the 1960s, with a progressive increase in outbreaks and human cases reported in Brazil and neighboring countries. In the Rio de Janeiro state, there has been a significant rise in suspected [...] Read more.

The Oropouche virus (OROV) has been circulating in the Amazon region since the 1960s, with a progressive increase in outbreaks and human cases reported in Brazil and neighboring countries. In the Rio de Janeiro state, there has been a significant rise in suspected cases of arboviruses, with only 30% of laboratory tests confirming infections with dengue, Zika, or chikungunya viruses. The investigation of OROV virus circulation in the Rio de Janeiro state was initiated and confirmed in April 2024. Our study aimed to retrospectively investigate OROV infections in dengue-suspected cases with inconclusive diagnosis in order to better understand the temporal and geographic introduction of OROV in the Rio de Janeiro state. Municipalities from Rio de Janeiro with arbovirus-like fever cases but a low percentage of dengue-positive RT-PCR test confirmations were identified in the laboratory database. Samples were selected for testing OROV infections using real-time RT-PCR as recommended by the Brazilian Ministry of Health. Municipalities in the Middle Paraíba region of the state showed 93% negative tests results for dengue, Zika, and chikungunya starting in September 2023. A total of 118 positive cases of Oropouche were recorded in the state of Rio de Janeiro between March and July 2024. Moreover, by genome sequencing of eight strains, it was shown that OROV circulating in Rio de Janeiro belongs to recently emergent M₁L₂S₂ lineage. Our findings retrospectively revealed a concentration of cases in the Middle Paraíba region and an outbreak in the rural village of Cacaria, located in the municipality of Piraí. According to our data, this region is the first area with sustained transmission in the Rio de Janeiro state. Full article

(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Control, and Future Directions)

► Show Figures

Figure 1

15 pages, 1806 KB

Open AccessEditor’s ChoiceArticle

Acute HSV-1 Ocular Infection Is Impaired in KLF15 Knockout Mice but Stress-Induced Reactivation from Latency Is Prolonged in Male KLF15 Knockout Mice

by Kelly S. Harrison and Clinton Jones

Pathogens 2025, 14(8), 823; https://doi.org/10.3390/pathogens14080823 - 20 Aug 2025

Cited by 1 | Viewed by 1789

Abstract

Acute human alpha-herpesvirus 1 (HSV-1) infection culminates in a latent infection of neurons in trigeminal ganglia (TG) and the central nervous system. Following infection of mucosal epithelial cells, certain neurons survive infection and life-long latency is established. Periodically, stressful stimuli trigger reactivation from [...] Read more.

Acute human alpha-herpesvirus 1 (HSV-1) infection culminates in a latent infection of neurons in trigeminal ganglia (TG) and the central nervous system. Following infection of mucosal epithelial cells, certain neurons survive infection and life-long latency is established. Periodically, stressful stimuli trigger reactivation from latency, which result in virus shedding, transmission to other people, and, occasionally, recurrent disease. The glucocorticoid receptor (GR) and Krüppel-like factor 15 (KLF15) comprise a feed-forward transcriptional loop that cooperatively transactivate key HSV-1 promoters that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. Silencing KLF15 significantly reduces HSV-1 replication in cultured mouse neuroblastoma cells. Consequently, we hypothesized that KLF15 mediates certain aspects of reactivation from latency. To test this hypothesis, we compared HSV-1 replication in KLF15^−/− mice versus wild-type (wt) parental C57BL/6 mice. Virus shedding during acute infection was reduced in KLF15^−/− mice. Male KLF15^−/− mice shed higher titers of virus during late stages of reactivation from latency compared to KLF15^−/− females and wt mice regardless of sex. At 15 d after explant-induced reactivation, virus shedding was higher in male KLF15^−/− mice relative to wt mice and female KLF15^−/− mice. These studies confirm KLF15 expression enhances viral replication during acute infection and reactivation from latency. Full article

(This article belongs to the Section Viral Pathogens)

► Show Figures

Figure 1

20 pages, 984 KB

Open AccessEditor’s ChoiceReview

Maternal HIV Infection and Antiretroviral Therapy in Pregnancy: Implications for Vertical Transmission, Fetal Safety, and Long-Term Infant Outcomes

by Tudor Fleșeriu, Lorena Elena Meliț, Cristina Oana Mărginean, Adrian Vlad Pop and Anca-Meda Văsieșiu

Pathogens 2025, 14(8), 818; https://doi.org/10.3390/pathogens14080818 - 19 Aug 2025

Cited by 2 | Viewed by 6019

Abstract

HIV mother-to-child transmission (MTCT) continues to pose a significant public health challenge, especially in regions with limited resources, although the worldwide distribution of antiretroviral therapy (ART) has drastically lowered the risk of vertical transmission to even below 1% in some regions. There are [...] Read more.

HIV mother-to-child transmission (MTCT) continues to pose a significant public health challenge, especially in regions with limited resources, although the worldwide distribution of antiretroviral therapy (ART) has drastically lowered the risk of vertical transmission to even below 1% in some regions. There are still uncertainties regarding the safety of some ART regimens during pregnancy and their longer-term effects on infants who are perinatally exposed to HIV but remain uninfected. This review explores current evidence regarding the interplay between maternal HIV infection, ART during pregnancy, and both maternal and pediatric outcomes. Particular attention is given to the risk/benefit ratio surrounding different drug classes, with integrase inhibitors seeming promising choices in MTCT due to their rapid viral suppression and favorable safety profiles. Meanwhile, regimens containing protease inhibitors or nucleoside reverse transcriptase inhibitors have been linked to some adverse outcomes such as low birth weight, growth restriction, and potential mitochondrial or metabolic disturbances. Although ART remains central in preventing MTCT, a deeper understanding of its effects on fetal development and postnatal health is needed, and it should be thoroughly monitored through future research and longitudinal surveillance. Full article

(This article belongs to the Special Issue Understanding HIV Pathogenesis and Targeting for the Prevention and Cure)

► Show Figures

Figure 1

21 pages, 4238 KB

Open AccessEditor’s ChoiceArticle

Relationship Between Cell Surface Viral Glycoprotein Expression and Resistance of Parainfluenza Virus Persistently Infected Cells to Complement-Mediated Lysis

by Nasser N. Yousef and Griffith D. Parks

Pathogens 2025, 14(8), 815; https://doi.org/10.3390/pathogens14080815 - 17 Aug 2025

Viewed by 989

Abstract

Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. The innate immune Complement (C′) pathways can recognize acute infected (AI) cells and result in their lysis, but the relative sensitivity of PI cells to C′-directed [...] Read more.

Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. The innate immune Complement (C′) pathways can recognize acute infected (AI) cells and result in their lysis, but the relative sensitivity of PI cells to C′-directed killing is incompletely understood. Here, we extended our previous studies on the interactions of C′ with parainfluenza virus AI and PI A549 cells to two additional respiratory tract cell lines. AI Hep2 and H1975 cells infected with Parainfluenza virus 5 (PIV5) were found to be highly sensitive to C′ lysis. By contrast, PIV5 PI cells were highly resistant to killing by C″. Surface deposition of membrane attack complex (MAC) and C3 was also greatly reduced on the surface of PI cells compared to AI cells. PI cells had lower levels of surface viral glycoprotein expression compared to AI cells. Treatment of AI cells with ribavirin (RBV) showed a dose-dependent decrease in both viral glycoprotein expression and sensitivity to C′-mediated lysis. When surface viral glycoprotein levels were reduced in AI cells to those in PI cells, AI cells became similarly resistant to C′. While sialic acid levels on PI cell surfaces matched that of naïve cells, enzymatic removal of this sialic acid did not increase sensitivity to C′-mediated lysis. Despite their varying profiles of C′ activation and deposition, these studies indicate downregulation of viral gene expression as a common mechanism of C′ resistance across various parainfluenza virus PI cell lines. Full article

(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)

► Show Figures

Figure 1

35 pages, 1649 KB

Open AccessEditor’s ChoiceReview

Candidemia: An Update on Epidemiology, Risk Factors, Diagnosis, Susceptibility, and Treatment

by Juan Pablo Cabrera-Guerrero, Eduardo García-Salazar, Graciela Hernandez Silva, Alberto Chinney Herrera, Erick Martínez-Herrera, Rodolfo Pinto-Almazán, María Guadalupe Frías-De-León and Carlos Alberto Castro-Fuentes

Pathogens 2025, 14(8), 806; https://doi.org/10.3390/pathogens14080806 - 14 Aug 2025

Cited by 4 | Viewed by 9389

Abstract

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression [...] Read more.

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression used in solid organ or hematopoietic transplantation, and neutropenia secondary to infectious or tumorous processes. Alterations in the gut microbiota in people living with HIV, caused by antiretroviral therapy, increase the possibility of colonization by C. albicans. Likewise, the presence of a central venous catheter, parenteral nutrition, and abdominal surgery stand out as the main risk factors for the development of candidemia. New diagnostic tools have been developed for the diagnosis of this mycosis that allow the identification of the main species, from improvements in conventional stains such as calcofluor white, which increases sensitivity, as well as technologies such as T2 Candida, MoiM assay, biomarker panel (1,3 β-D-glucan, C-reactive protein, presepsin, and procalcitonin), and, more recently, the development of biosensors for the identification of Candida spp. Regarding treatment, the use of micafungin and anidulafungin in patients with obesity defined by a BMI > 30 kg/m² has shown higher survival rates and therapeutic success. Meanwhile, newer antifungals such as rezafungin and fosmanogepix have demonstrated excellent results in the treatment of these patients. Therefore, this review aims to update the epidemiology and risk factors of candidemia, as well as analyze the diagnostic tools and treatments currently available. Full article

(This article belongs to the Special Issue An Update on Fungal Infections)

► Show Figures

Figure 1

14 pages, 1026 KB

Open AccessEditor’s ChoiceArticle

Targeted Whole Genome Sequencing of African Swine Fever Virus and Classical Swine Fever Virus on the MinION Portable Sequencing Platform

by Chester D. McDowell, Taeyong Kwon, Patricia Assato, Emily Mantlo, Jessie D. Trujillo, Natasha N. Gaudreault, Leonardo C. Caserta, Igor Morozov, Jayme A. Souza-Neto, Roman M. Pogranichniy, Diego G. Diel and Juergen A. Richt

Pathogens 2025, 14(8), 804; https://doi.org/10.3390/pathogens14080804 - 13 Aug 2025

Cited by 1 | Viewed by 2035

Abstract

African swine fever virus (ASFV) and classical swine fever virus (CSFV) are important transboundary animal diseases (TADs) affecting swine. ASFV is a large DNA virus with a genome size of 170–190+ kilobases (kB) belonging to the family Asfarviridae, genus Asfivirus. CSFV is [...] Read more.

African swine fever virus (ASFV) and classical swine fever virus (CSFV) are important transboundary animal diseases (TADs) affecting swine. ASFV is a large DNA virus with a genome size of 170–190+ kilobases (kB) belonging to the family Asfarviridae, genus Asfivirus. CSFV is a single-stranded RNA virus with a genome size of approximately 12 kB, belonging to the family Flaviviridae, genus Pestivirus. Outbreaks involving either one of these viruses result in similar disease syndromes and significant economic impacts from: (i) high morbidity and mortality events; (ii) control measures which include culling and quarantine; and (iii) export restrictions of swine and pork products. Current detection methods during an outbreak provide minimal genetic information on the circulating virus strains/genotypes that are important for tracing and vaccine considerations. The increasing availability and reduced cost of next-generation sequencing (NGS) allow for the establishment of NGS protocols for the rapid identification and complete genetic characterization of outbreak strains during an investigation. NGS data provides a better understanding of viral spread and evolution, facilitating the development of novel and effective control measures. In this study, panels of primers spanning the genomes of ASFV and CSFV were independently developed to generate approximately 10 kB and 6 kB amplicons, respectively. The primer panels consisted of 19 primer pairs for ASFV and 2 primer pairs for CSFV, providing whole genome amplification of each pathogen. These primer pools were further optimized for batch pooling and thermocycling conditions, resulting in a total of 5 primer pools/reactions used for ASFV and 2 primer pairs/reactions for CSFV. The ASFV primer panel was tested on viral DNA extracted from blood collected from pigs experimentally infected with ASFV genotype I and genotype II viruses. The CSFV primer panel was tested on 11 different strains of CSFV representing the three known CSFV genotypes, and 21 clinical samples collected from pigs experimentally infected with two different genotype 1 CSF viruses. ASFV and CSFV amplicons from optimized PCR were subsequently sequenced on the Oxford Nanopore MinION platform. The targeted protocols for these viruses resulted in an average coverage greater than 1,000X for ASFV, with 99% of the genome covered, and 10,000X–20,000X for CSFV, with 97% to 99% of the genomes covered. The ASFV targeted whole genome sequencing protocol has been optimized for genotype II ASF viruses that have been responsible for the more recent outbreaks outside of Africa. The CSFV targeted whole genome sequencing protocol has universal applications for the detection of all CSFV genotypes. Protocols developed and evaluated here will be essential complementary tools for early pathogen detection and differentiation, as well as genetic characterization of these high-consequence swine viruses, globally and within the United States, should an outbreak occur. Full article

(This article belongs to the Section Viral Pathogens)

► Show Figures

Figure 1

13 pages, 2897 KB

Open AccessEditor’s ChoiceArticle

Ancient Origins and Global Diversity of Plague: Genomic Evidence for Deep Eurasian Reservoirs and Recurrent Emergence

by Subhajeet Dutta, Aditya Upadhyay, Swamy R. Adapa, Gregory O’Corry-Crowe, Sucheta Tripathy and Rays H. Y. Jiang

Pathogens 2025, 14(8), 797; https://doi.org/10.3390/pathogens14080797 - 9 Aug 2025

Cited by 1 | Viewed by 5157

Abstract

Yersinia pestis, the causative agent of plague, has triggered multiple pandemics throughout human history, yet its long-term evolutionary patterns and reservoir dynamics remain poorly understood. Here, we present a global phylogenomic analysis of ancient and modern Y. pestis strains spanning from the [...] Read more.

Yersinia pestis, the causative agent of plague, has triggered multiple pandemics throughout human history, yet its long-term evolutionary patterns and reservoir dynamics remain poorly understood. Here, we present a global phylogenomic analysis of ancient and modern Y. pestis strains spanning from the Neolithic and Bronze Age to the present day. We show that pandemic-causing lineages did not arise from a single ancestral strain but instead emerged independently along deep branches of the Y. pestis phylogeny. Pandemic-associated Y. pestis strains were recovered exclusively from human remains and display clear local temporal divergence, indicating evolution driven by human transmission during outbreaks. These findings support the hypothesis that plague emergence is driven by complex, regionally rooted reservoirs, with recurrent spillovers into human populations across millennia. Our work highlights the need to view plague not as a series of isolated outbreaks but as a long-standing zoonotic threat shaped by deep evolutionary history, host ecology, and human societal structures. Full article

(This article belongs to the Special Issue Bacterial Pathogens—Strategies for Dissemination, Infection, and Persistence Within a Host)

► Show Figures

Figure 1

13 pages, 1921 KB

Open AccessEditor’s ChoiceArticle

Antiviral Activity of Haematococcus pluvialis Algae Extract Is Not Exclusively Due to Astaxanthin

by Paula Peinsipp, Tanja Gerlza, Julia Kircher, Kurt Zatloukal, Corinna Jäger, Peter Pucher and Andreas J. Kungl

Pathogens 2025, 14(8), 791; https://doi.org/10.3390/pathogens14080791 - 7 Aug 2025

Cited by 2 | Viewed by 1875

Abstract

In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We [...] Read more.

In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We therefore hypothesized that the compound’s beneficial effects are not only related to astaxanthin. Thus, a “green” algae extract (i.e., poor astaxanthin content < 0.2%; ASX^p) of the microalgae Haematococcus pluvialis, as well as an astaxanthin-rich algae extract (astaxanthin content = 20%; ASX^r), were tested in in vitro cellular viral infection assays. Thereby, it was found that both extracts reduced viral infections significantly. As a potential mode of inhibitory action, the binding of ASX-oleoresin to the viral spike protein was investigated by isothermal fluorescence titration, revealing binding affinities of Kd = 1.05 µM for ASX^r and Kd = 1.42 µM for ASX^p. Based on our data, we conclude that several ASX-oleoresin fractions from H. pluvialis exhibit antiviral activity, which extends beyond the known antioxidant activity of astaxanthin. From a molecular dynamic simulation of ASX-oleoresin, fatty acid domains could be considered as activity-chaperoning factors of ASX. Therefore, microalgae biomass should be considered in the future for further antiviral activities. Full article

(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)

► Show Figures

Figure 1

11 pages, 2360 KB

Open AccessEditor’s ChoiceArticle

First Survey on the Seroprevalence of Coxiella burnetii in Positive Human Patients from 2015 to 2024 in Sardinia, Italy

by Cinzia Santucciu, Maria Paola Giordo, Antonio Tanda, Giovanna Chessa, Matilde Senes, Gabriella Masu, Giovanna Masala and Valentina Chisu

Pathogens 2025, 14(8), 790; https://doi.org/10.3390/pathogens14080790 - 7 Aug 2025

Cited by 2 | Viewed by 944

Abstract

Coxiella burnetii, the etiological agent of Q fever, is a globally distributed zoonotic pathogen affecting both animals and humans. Despite its known endemicity in various Mediterranean regions, data on human seroprevalence in Sardinia are still lacking. This study aimed to assess seroprevalence [...] Read more.

Coxiella burnetii, the etiological agent of Q fever, is a globally distributed zoonotic pathogen affecting both animals and humans. Despite its known endemicity in various Mediterranean regions, data on human seroprevalence in Sardinia are still lacking. This study aimed to assess seroprevalence in patients and to analyze the annual positivity rate related to the serum samples collected in Sardinia over a ten-year period (2015–2024). For this purpose, a total of 1792 patients were involved in the survey, and 4310 serum samples were analyzed using indirect immunofluorescence assay (IFI) to detect IgM and IgG antibodies against C. burnetii. The global seroprevalence rates relating to all the patients over a ten-year period were determined along with the annual positivity rate and trends from all sera. An overall seroprevalence of 27.0% and an average of annual positivity rate of 16.0% were determined, with the IFI detecting IgG antibodies in 15.2% of positive samples and IgM antibodies in 0.9%, suggesting significant prior exposure of the population evaluated. Annual positivity rates ranged from 24.8% in 2016 to 8.0% in 2020. These results confirmed the endemic circulation of C. burnetii in Sardinia and the ongoing risk of human exposure. A GIS-based map was built to evidence the spatial distribution of Q fever in Sardinia. Interestingly, areas with higher seroprevalence appear to coincide with the distribution of sheep and goat farms, indicating a link between livestock and human exposure. These findings confirm the circulation of C. burnetii in Sardinia and underscore the importance of epidemiological monitoring, public health interventions, and educational efforts in populations at increased risk. Full article

(This article belongs to the Section Bacterial Pathogens)

► Show Figures

Figure 1

17 pages, 1027 KB

Open AccessEditor’s ChoiceReview

Chimeric Antigen Receptor Immunotherapy for Infectious Diseases: Current Advances and Future Perspectives

by Maria Kourti, Paschalis Evangelidis, Emmanuel Roilides and Elias Iosifidis

Pathogens 2025, 14(8), 774; https://doi.org/10.3390/pathogens14080774 - 5 Aug 2025

Cited by 3 | Viewed by 2277

Abstract

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and [...] Read more.

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article

(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)

► Show Figures

Figure 1

18 pages, 1645 KB

Open AccessEditor’s ChoiceArticle

Assessing Zoonotic Risks of Blastocystis Infection in Singapore

by Thet Tun Aung, Charlotte Kai Qi How, Jean-Marc Chavatte, Nazmi Bin Nazir, Edgar Macabe Pena, Bryan Ogden, Grace Rou’en Lim, Yasmina Arditi Paramastri, Lois Anne Zitzow, Hanrong Chen, Niranjan Nagarajan, Kevin Shyong Wei Tan and Benoit Malleret

Pathogens 2025, 14(8), 773; https://doi.org/10.3390/pathogens14080773 - 5 Aug 2025

Cited by 1 | Viewed by 1231

Abstract

Blastocystis spp. is an enteric protist that is present worldwide. Despite being discovered a century ago, there is still much to be learned about its pathogenicity and transmission. Different subtypes (ST) of Blastocystis spp. have been identified in various hosts, including humans, birds, [...] Read more.

Blastocystis spp. is an enteric protist that is present worldwide. Despite being discovered a century ago, there is still much to be learned about its pathogenicity and transmission. Different subtypes (ST) of Blastocystis spp. have been identified in various hosts, including humans, birds, and insects, and there is potential for zoonotic transmission through contact between humans and animals. The prevalence of Blastocystis spp. in humans and macaques in Singapore was understudied, and the findings revealed a significant prevalence of the parasite, with rates of 90% and 100% observed in each respective Macaca fascicularis population 1 and 2, with main subtypes (ST1, ST2, ST3, and ST5). Using metagenomics, the different subtypes of Blastocystis spp. (comprising ST2, ST3, and ST17) were identified in a healthy Singaporean cohort. Additionally, seven incidental findings of Blastocystis spp. were discovered in human patients with other gut parasites, including two ST1, two ST2, two ST3, and one ST8. Several factors such as diet or reverse zoonotic transmission are suggested to play a role in Blastocystis sp. subtype distribution. Full article

(This article belongs to the Section Parasitic Pathogens)

► Show Figures

Figure 1

15 pages, 7335 KB

Open AccessEditor’s ChoiceArticle

Osage Orange (Maclura pomifera) and Spearmint (Mentha spicata) Leaf Extracts Exhibit Antibacterial Activity and Inhibit Human Respiratory Syncytial Virus (hRSV)

by Milica Nenadovich, Molly Kubal, Maci R. Hopp, Abigail D. Crawford, Megan E. Hardewig, Madison G. Sedlock, Rida Jawad, Zarrar A. Khan, Adrianna M. Smith, Mia A. Mroueh, Matthew DuBrava, Ellie C. Jones, Cael Rahe, Sean T. Berthrong, Anne M. Wilson, Michael P. Trombley, Ashlee H. Tietje and Christopher C. Stobart

Pathogens 2025, 14(8), 776; https://doi.org/10.3390/pathogens14080776 - 5 Aug 2025

Viewed by 1652

Abstract

The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous [...] Read more.

The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous leaf extracts from two plants commonly found in North America, Osage orange (M. pomifera) and spearmint (M. spicata). Both extracts exhibited no significant cytotoxic or morphologic impact on HEp-2 human cancer cells up to 25 mg/mL. However, both extracts demonstrated strong dose-dependent antibacterial activity, significantly inhibiting replication of E. coli and S. aureus at concentrations ≥ 1 mg/mL. Antiviral assays revealed that both extracts inhibited hRSV infectivity, with spearmint extract showing higher potency (EC₅₀ = 1.01 mg/mL) compared to Osage orange (EC₅₀ = 3.85 mg/mL). Gas chromatography–mass spectrometry (GC-MS) identified three major extract constituents: 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol (Osage orange), and R-(-)-carvone (spearmint). Among these, only carvone significantly inhibited hRSV in vitro, suggesting its key role in spearmint’s antiviral activity. These findings highlight the therapeutic potential of Osage orange and spearmint leaf extracts, particularly as sources of water-soluble compounds with antimicrobial properties, and support further investigation into their mechanisms of action and broader clinical relevance. Full article

(This article belongs to the Special Issue Epidemiology of Respiratory Syncytial Virus and Potential Public Health Impact of Vaccination)

► Show Figures

Figure 1

28 pages, 1577 KB

Open AccessEditor’s ChoiceArticle

Prevalence of Anti-Anisakis simplex Antibodies in a Cohort of Patients with Inflammatory Bowel Disease in Norway

by María P. de la Hoz-Martín, Juan González-Fernández, Juan Carlos Andreu-Ballester, Marte L. Hoivik, Petr Ricanek, Torunn Bruland, Arne K. Sandvik, Carmen Cuéllar and Ignacio Catalán-Serra

Pathogens 2025, 14(8), 769; https://doi.org/10.3390/pathogens14080769 - 4 Aug 2025

Cited by 1 | Viewed by 1359

Abstract

This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in [...] Read more.

This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in IBD were also explored. A total of 86 UC patients, 68 CD patients, and 41 healthy controls were prospectively enrolled from four Norwegian hospitals (2013–2022). Diagnosis and disease activity were established using standard clinical, endoscopic, and biomarker criteria. Serum samples were analyzed for total Ig, IgG, IgM, IgA, and IgE antibodies against A. simplex and Pseudoterranova decipiens using ELISA. Anti-A. simplex IgG seroprevalence was 4.9% in controls and 3.2% in IBD (3.5% UC, 2.9% CD). IgM seroprevalence was 0% in all groups. IgA seroprevalence was higher in IBD (16.2%) than controls (4.9%), with 14.0% in UC and 19.1% in CD. IgE seroprevalence was low across all groups. Smoking correlated with lower antibody levels and higher surgery rates. In UC, higher anti-A. simplex IgG and IgE levels were associated with milder disease and better prognosis. Anti-TNFα and azathioprine treatments were linked to higher anti-A. simplex IgA. Norwegian UC and CD patients had significantly higher anti-A. simplex total Ig and IgA seroprevalence than healthy controls, indicating increased exposure or immune response. Anti-A. simplex IgG and IgE may serve as markers of clinical activity in UC. Further research is warranted to clarify the clinical significance of these findings. Full article

(This article belongs to the Section Parasitic Pathogens)

► Show Figures

Graphical abstract

46 pages, 1120 KB

Open AccessEditor’s ChoiceReview

From Morphology to Multi-Omics: A New Age of Fusarium Research

by Collins Bugingo, Alessandro Infantino, Paul Okello, Oscar Perez-Hernandez, Kristina Petrović, Andéole Niyongabo Turatsinze and Swarnalatha Moparthi

Pathogens 2025, 14(8), 762; https://doi.org/10.3390/pathogens14080762 - 1 Aug 2025

Cited by 6 | Viewed by 5097

Abstract

The Fusarium genus includes some of the most economically and ecologically impactful fungal pathogens affecting global agriculture and human health. Over the past 15 years, rapid advances in molecular biology, genomics, and diagnostic technologies have reshaped our understanding of Fusarium taxonomy, host–pathogen dynamics, [...] Read more.

The Fusarium genus includes some of the most economically and ecologically impactful fungal pathogens affecting global agriculture and human health. Over the past 15 years, rapid advances in molecular biology, genomics, and diagnostic technologies have reshaped our understanding of Fusarium taxonomy, host–pathogen dynamics, mycotoxin biosynthesis, and disease management. This review synthesizes key developments in these areas, focusing on agriculturally important Fusarium species complexes such as the Fusarium oxysporum species complex (FOSC), Fusarium graminearum species complex (FGSC), and a discussion on emerging lineages such as Neocosmospora. We explore recent shifts in species delimitation, functional genomics, and the molecular architecture of pathogenicity. In addition, we examine the global burden of Fusarium-induced mycotoxins by examining their prevalence in three of the world’s most widely consumed staple crops: maize, wheat, and rice. Last, we also evaluate contemporary management strategies, including molecular diagnostics, host resistance, and integrated disease control, positioning this review as a roadmap for future research and practical solutions in Fusarium-related disease and mycotoxin management. By weaving together morphological insights and cutting-edge multi-omics tools, this review captures the transition into a new era of Fusarium research where integrated, high-resolution approaches are transforming diagnosis, classification, and management. Full article

(This article belongs to the Special Issue Current Research on Fusarium: 2nd Edition)

► Show Figures

Figure 1

25 pages, 9193 KB

Open AccessEditor’s ChoiceArticle

Antibiotic-Loaded Bioglass 45S5 for the Treatment and Prevention of Staphylococcus aureus Infections in Orthopaedic Surgery: A Novel Strategy Against Antimicrobial Resistance

by Humera Sarwar, Richard A. Martin, Heather M. Coleman, Aaron Courtenay and Deborah Lowry

Pathogens 2025, 14(8), 760; https://doi.org/10.3390/pathogens14080760 - 1 Aug 2025

Viewed by 1592

Abstract

This study explores the potential of biodegradable Bioglass 45S5 formulations as a dual-function approach for preventing and treating Staphylococcus aureus infections in orthopaedic surgery while addressing the growing concern of antimicrobial resistance (AMR). The research focuses on the development and characterisation of antibiotic-loaded [...] Read more.

This study explores the potential of biodegradable Bioglass 45S5 formulations as a dual-function approach for preventing and treating Staphylococcus aureus infections in orthopaedic surgery while addressing the growing concern of antimicrobial resistance (AMR). The research focuses on the development and characterisation of antibiotic-loaded BG45S5 formulations, assessing parameters such as drug loading efficiency, release kinetics, antimicrobial efficacy, and dissolution behaviour. Key findings indicate that the F2l-BG45S5-T-T-1.5 and F2l-BG45S5-T-V-1.5 formulations demonstrated controlled antibiotic release for up to seven days, with size distributions of D(10): 7.11 ± 0.806 µm, 4.96 ± 0.007 µm; D(50): 25.34 ± 1.730 µm, 25.20.7 ± 0.425 µm; and D(90): 53.7 ± 7.95 µm, 56.10 ± 0.579 µm, respectively. These formulations facilitated hydroxyapatite formation on their surfaces, indicative of osteogenic potential. The antimicrobial assessments revealed zones of inhibition against methicillin-susceptible Staphylococcus aureus (MSSA, ATCC-6538) measuring 20.3 ± 1.44 mm and 24.6 ± 1.32 mm, while for methicillin-resistant Staphylococcus aureus (MRSA, ATCC-43300), the inhibition zones were 21.6 ± 1.89 mm and 22 ± 0.28 mm, respectively. Time-kill assay results showed complete bacterial eradication within eight hours. Additionally, biocompatibility testing via MTT assay confirmed cell viability of >75%. In conclusion, these findings highlight the promise of antibiotic-loaded BG45S5 as a multifunctional biomaterial capable of both combating bone infections and supporting bone regeneration. These promising results suggest that in vivo studies should be undertaken to expedite these materials into clinical applications. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in the Post-COVID Era: A Silent Pandemic)

► Show Figures

Figure 1

25 pages, 5521 KB

Open AccessEditor’s ChoiceArticle

Trypanosoma cruzi Growth Is Impaired by Oleoresin and Leaf Hydroalcoholic Extract from Copaifera multijuga in Human Trophoblast and Placental Explants

by Guilherme de Souza, Clara Peleteiro Teixeira, Joed Pires de Lima Júnior, Marcos Paulo Oliveira Almeida, Marina Paschoalino, Luana Carvalho Luz, Natália Carine Lima dos Santos, Rafael Martins de Oliveira, Izadora Santos Damasceno, Matheus Carvalho Barbosa, Guilherme Vieira Faria, Maria Anita Lemos Vasconcelos Ambrosio, Rodrigo Cassio Sola Veneziani, Jairo Kenupp Bastos, Angelica Oliveira Gomes, Rosiane Nascimento Alves, Carlos Henrique Gomes Martins, Samuel Cota Teixeira, Eloisa Amália Vieira Ferro and Bellisa Freitas Barbosa

Pathogens 2025, 14(8), 736; https://doi.org/10.3390/pathogens14080736 - 25 Jul 2025

Cited by 1 | Viewed by 888

Abstract

Congenital Chagas disease (CCD) is caused when Trypanosoma cruzi crosses the placental barrier during pregnancy and reaches the fetus, which can lead to serious consequences in the developing fetus. Current treatment is carried out with nifurtimox or benznidazole, but their effectiveness is limited, [...] Read more.

Congenital Chagas disease (CCD) is caused when Trypanosoma cruzi crosses the placental barrier during pregnancy and reaches the fetus, which can lead to serious consequences in the developing fetus. Current treatment is carried out with nifurtimox or benznidazole, but their effectiveness is limited, and they cause side effects, requiring the search for new therapeutic strategies. In this sense, many studies have demonstrated the potential of different compounds of the Copaifera genus in the control of parasitic diseases. Here, we aimed to evaluate the effect of oleoresin (OR) and leaf hydroalcoholic extract (LHE) of Copaifera multijuga on Trypanosoma cruzi infection in human villous trophoblast cells (BeWo line) and human placenta explants. Treatment with both compounds reduced invasion, proliferation, and release of trypomastigotes. Furthermore, OR and LHE affected the trypomastigotes and amastigote morphology, compromising their ability to invade and proliferate in BeWo cells, respectively. Also, treatment with OR decreased ROS production in infected BeWo cells, while LHE induced an increase. In addition, both compounds induced pro-inflammatory and anti-inflammatory cytokine production. In human placental explants, both compounds also decreased T. cruzi infection, in addition to inducing the production of pro-inflammatory cytokines. Thus, both OR and LHE of C. multijuga control T. cruzi infection at the human maternal–fetal interface, highlighting the possible therapeutic potential of these compounds for the treatment of CCD. Full article

(This article belongs to the Special Issue Exploring Natural Products as Antiparasitic Agents: Efficacy Against Parasites of Veterinary and Public Health Significance)

► Show Figures

Graphical abstract

14 pages, 722 KB

Open AccessEditor’s ChoiceArticle

When the Last Line Fails: Characterization of Colistin-Resistant Acinetobacter baumannii Reveals High Virulence and Limited Clonal Dissemination in Greek Hospitals

by Dimitrios Karakalpakidis, Theofilos Papadopoulos, Michalis Paraskeva, Michaela-Eftychia Tsitlakidou, Eleni Vagdatli, Helen Katsifa, Apostolos Beloukas, Charalampos Kotzamanidis and Christine Kottaridi

Pathogens 2025, 14(8), 730; https://doi.org/10.3390/pathogens14080730 - 24 Jul 2025

Cited by 4 | Viewed by 2941

Abstract

Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and [...] Read more.

Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and genomic characteristics of all multidrug-resistant A. baumannii isolates collected between January and June 2022 from two tertiary care hospitals in Thessaloniki, Greece. A total of 40 isolates were included. All isolates exhibited resistance to colistin; however, none harbored the mcr-1 to mcr-9 genes, as confirmed by polymerase chain reaction (PCR). PCR-based screening for virulence-associated genes revealed high prevalence rates of basD (100%), pld (95%), csuE (87.5%), and bap (77.5%). In contrast, ompA and pglC were not detected. Twitching motility ranged from 2 to 50 mm, with 25% of the isolates classified as non-motile and 20% as highly motile. Swarming motility was observed in all strains. Additionally, all isolates demonstrated positive α-hemolysis, suggesting a potential virulence mechanism involving tissue damage and iron acquisition. Pulsed-field gel electrophoresis (PFGE) revealed significant genomic diversity among the isolates, indicating a low likelihood of patient-to-patient or clonal transmission within the hospital setting. These findings highlight the complex relationship between antimicrobial resistance and virulence in clinical A. baumannii isolates and emphasize the urgent need for robust infection control strategies and continued microbiological surveillance. Full article

(This article belongs to the Special Issue Acinetobacter baumannii: An Emerging Pathogen)

► Show Figures

Figure 1

14 pages, 2694 KB

Open AccessEditor’s ChoiceArticle

Functional Amyloids in Adhesion of Non-albicans Candida Species

by Melissa C. Garcia-Sherman, Safraz A. Hamid, Desmond N. Jackson, James Thomas and Peter N. Lipke

Pathogens 2025, 14(8), 723; https://doi.org/10.3390/pathogens14080723 - 22 Jul 2025

Viewed by 1367

Abstract

Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. [...] Read more.

Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. Many of the adhesins contain cross-β core sequences that form amyloid-like protein aggregates on the fungal surface. The aggregates mediate high-avidity bonding that contributes to biofilm establishment and persistence. Accordingly, autopsy sections from individuals with candidiasis and other mycoses have amyloids within abscesses. An amyloid-forming peptide containing a sequence from Candida albicans Als5 bound to C. albicans, C. tropicalis, and C. parapsilosis. C. albicans and C. tropicalis aggregated with beads coated with serum albumin, and the aggregates stained with the amyloid-binding dye thioflavin T. Additionally, an Als5-derived amyloid-inhibiting peptide blocked cell aggregation. The amyloid-inhibiting peptide also blocked C. albicans, C. tropicalis, and C. parapsilosis adhesion to monolayers of FaDu epithelial cells. These results show the involvement of amyloid-like interactions in pathogenesis in several Candida species. Full article

(This article belongs to the Special Issue The Dark Side of Fungi: Exploring Pathogenesis in Candida and Other Fungal Pathogens)

► Show Figures

Graphical abstract

13 pages, 901 KB

Open AccessEditor’s ChoiceArticle

Efficacy and Safety of an Oxalic Acid and Glycerin Formulation for Varroa destructor Control in Honey Bee Colonies During Summer in a Northern Climate

by Daniel Thurston, Les Eccles, Melanie Kempers, Daniel Borges, Kelsey Ducsharm, Lynae Ovinge, Dave Stotesbury, Rod Scarlett, Paul Kozak, Tatiana Petukhova, Ernesto Guzman-Novoa and Nuria Morfin

Pathogens 2025, 14(8), 724; https://doi.org/10.3390/pathogens14080724 - 22 Jul 2025

Cited by 4 | Viewed by 5989

Abstract

Effective control of the parasitic mite Varroa destructor in honey bee (Apis mellifera) colonies relies on integrated pest management (IPM) strategies to prevent mite populations from reaching economic injury levels. Formulations of oxalic acid combined with glycerin may provide a viable [...] Read more.

Effective control of the parasitic mite Varroa destructor in honey bee (Apis mellifera) colonies relies on integrated pest management (IPM) strategies to prevent mite populations from reaching economic injury levels. Formulations of oxalic acid combined with glycerin may provide a viable summer treatment option in continental Northern climates. This study evaluated the efficacy of oxalic acid and glycerin strips compared to oxalic acid dribble and 65% formic acid when applied in mid-August. Mite levels and colony health parameters were assessed, and honey samples from oxalic acid-treated colonies were analyzed for residue levels. Results showed that the oxalic acid and glycerin strips had a moderate acaricidal efficacy (55.8 ± 3.2%), which was significantly higher than those of 65% formic acid (42.6 ± 3.2%) and oxalic acid dribble (39.5 ± 4.3%), which did not differ between them, suggesting potential for summer mite control. No significant adverse effects on cluster size, worker mortality, queen status, or colony survival were observed. Oxalic acid and glycerin increased the proportion of spotty brood patterns at early timepoints after treatment, but recovery was noted after 45 days of starting the treatment. Similar effects on brood were observed with 65% formic acid 14 days after starting the treatment, with recovery by 28 and 45 days after starting the treatment. No significant differences in oxalic acid residues in honey from the control and treatment colonies were found. Oxalic acid and glycerin strips might help control varroa mite populations, delaying their exponential growth and helping reduce economic losses for beekeepers, but this treatment should be considered as part of an IPM strategy and not a stand-alone method for V. destructor control. Full article

(This article belongs to the Special Issue Surveillance, Detection and Control of Infectious Diseases of Bees)

► Show Figures

Figure 1

17 pages, 363 KB

Open AccessEditor’s ChoiceSystematic Review

Efficacy of GS-441524 for Feline Infectious Peritonitis: A Systematic Review (2018–2024)

by Emma Gokalsing, Joana Ferrolho, Mark S. Gibson, Hugo Vilhena and Sofia Anastácio

Pathogens 2025, 14(7), 717; https://doi.org/10.3390/pathogens14070717 - 19 Jul 2025

Cited by 4 | Viewed by 8716

Abstract

Feline infectious peritonitis (FIP) is a severe viral disease with a very high fatality rate. GS-441524 is an adenosine analogue that acts as an antiviral and has shown promise in FIP treatment. However, its commercialization in some regions is not yet authorized. To [...] Read more.

Feline infectious peritonitis (FIP) is a severe viral disease with a very high fatality rate. GS-441524 is an adenosine analogue that acts as an antiviral and has shown promise in FIP treatment. However, its commercialization in some regions is not yet authorized. To evaluate the efficacy of GS-441524 based on the published literature, a systematic review was conducted. This systematic review was conducted using PubMed, ScienceDirect, and Google Scholar for studies published from 2018 onwards. Following PRISMA guidelines, 11 studies (totaling 650 FIP cases treated with GS-441524 alone or in combination) were included. Therapeutic efficacy was assessed by FIP form, clinical signs, and dosage. The overall treatment success rate was 84.6%. This rate was higher when GS-441524 was combined with other antivirals and lower in cases of wet FIP or those with neurological complications. Combination therapy with other antivirals may improve outcomes in complicated FIP cases, although further studies are needed. The GS-441524 dosages associated with the best outcomes were 5–10 mg/kg once daily (or equivalent subcutaneous dose), adjusted for FIP type, severity, and presence of neurological/ocular signs. Higher dosages can be used for severe cases or to prevent relapse, but splitting into twice-daily dosing may be necessary to avoid absorption issues. In summary, this synthesis indicates that GS-441524 is a highly promising treatment for FIP, with a high success rate among treated cases. Nevertheless, randomized controlled trials are needed to establish evidence-based therapeutic protocols tailored to different FIP presentations. Full article

► Show Figures

Figure 1

16 pages, 2557 KB

Open AccessEditor’s ChoiceArticle

Surveillance of Salmonella Serovars in the Food Chain in Poland: A Five-Year Review (2016–2020)

by Ewelina Skrzypiec, Magdalena Skarżyńska, Magdalena Zając, Renata Kwit, Anna Lalak, Aleksandra Śmiałowska-Węglińska, Emilia Mikos-Wojewoda, Paulina Pasim, Weronika Koza, Dominika Wojdat, Inga Bona, Dominika Pastuszka, Sylwia Hudzik-Pałosz and Dariusz Wasyl

Pathogens 2025, 14(7), 712; https://doi.org/10.3390/pathogens14070712 - 18 Jul 2025

Cited by 1 | Viewed by 1106

Abstract

(1) Background: Understanding the distribution of Salmonella serovars in food, animals, and their environments is crucial for identifying infection sources and monitoring pathogen prevalence in the food chain. This study analysed Salmonella serovars in Poland from 2016 to 2020, focusing on their epidemiological [...] Read more.

(1) Background: Understanding the distribution of Salmonella serovars in food, animals, and their environments is crucial for identifying infection sources and monitoring pathogen prevalence in the food chain. This study analysed Salmonella serovars in Poland from 2016 to 2020, focusing on their epidemiological significance. (2) Methods: Isolation of Salmonella was carried out following PN-EN ISO 6579 standards, and serotyping was performed using the White–Kauffmann–Le Minor scheme. A total of 7104 isolates were collected from food-producing animals, their environments, food of animal origin, feedingstuffs, and fertilisers. (3) Results: A total of 175 serovars were identified, with S. Enteritidis (n = 2905; 40.9%), S. Infantis (n = 1167; 16.4%), and S. Typhimurium (n = 360; 5.1%) being the most prevalent. Species-specific patterns were observed: S. Enteritidis dominated in chickens, ducks, and cattle; S. Kentucky in turkeys; S. Typhimurium in geese; and monophasic S. Typhimurium in pigs. S. Enteritidis and S. Infantis were most frequent in food of animal origin, especially broiler meat. In feedingstuffs, S. Agona was predominant, while fertilisers mostly contained S. Derby and S. Infantis. (4) Conclusions: The study highlights the source-dependent variety of Salmonella serovars and the importance of serotyping in tracing infection routes and preventing the spread of pathogens. Identifying the most common serovars supports the development of targeted preventive measures, including improved biosecurity, hygiene, and management practices to enhance food safety. Full article

► Show Figures

Figure 1

21 pages, 8833 KB

Open AccessEditor’s ChoiceArticle

Harnessing Hazara Virus as a Surrogate for Crimean–Congo Hemorrhagic Fever Virus Enables Inactivation Studies at a Low Biosafety Level

by Judith Olejnik, Kristina Meier, Jarod N. Herrera, Daniel J. DeStasio, Dylan J. Deeney, Elizabeth Y. Flores, Mitchell R. White, Adam J. Hume and Elke Mühlberger

Pathogens 2025, 14(7), 700; https://doi.org/10.3390/pathogens14070700 - 15 Jul 2025

Cited by 1 | Viewed by 1567

Abstract

Research on highly pathogenic biosafety level 4 (BSL-4) viruses that are classified as Select Agents involves transferring inactivated materials to lower containment levels for further analysis. Compliance with Select Agent and BSL-4 safety regulations necessitates the validation and verification of inactivation procedures. To [...] Read more.

Research on highly pathogenic biosafety level 4 (BSL-4) viruses that are classified as Select Agents involves transferring inactivated materials to lower containment levels for further analysis. Compliance with Select Agent and BSL-4 safety regulations necessitates the validation and verification of inactivation procedures. To streamline this process, it would be beneficial to use surrogate BSL-2 viruses for inactivation studies. This not only simplifies BSL-4 work but also enables the testing and validation of inactivation procedures in research facilities that lack access to high-containment laboratories yet may receive samples containing highly pathogenic viruses that require efficient and complete inactivation. In this study, we used Hazara virus (HAZV) as a surrogate virus for Crimean–Congo hemorrhagic fever virus to show the efficacy of various inactivation methods. We demonstrate the successful inactivation of HAZV using TRIzol/TRIzol LS and aldehyde fixation. Importantly, the parameters of the aldehyde inactivation of cell pellets differed from those of the monolayers, highlighting the importance of inactivation validation. As part of this study, we also defined specific criteria that must be met by a BSL-2 virus to be used as a surrogate for a closely related BSL-4 virus. Defining these criteria helps identify suitable nonpathogenic surrogates for developing inactivation procedures for highly pathogenic viruses. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Molecular Epidemiology, Diagnostics and Management of Viral Pathogens)

► Show Figures

Figure 1

12 pages, 247 KB

Open AccessEditor’s ChoiceArticle

Restoring Control: Real-World Success with Imipenem–Relebactam in Critical MDR Infections—A Multicenter Observational Study

by Andrea Marino, Giuseppe Pipitone, Emmanuele Venanzi Rullo, Federica Cosentino, Rita Ippolito, Roberta Costa, Sara Bagarello, Ylenia Russotto, Chiara Iaria, Bruno Cacopardo and Giuseppe Nunnari

Pathogens 2025, 14(7), 685; https://doi.org/10.3390/pathogens14070685 - 11 Jul 2025

Cited by 3 | Viewed by 2150

Abstract

Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but [...] Read more.

Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. Full article

(This article belongs to the Special Issue Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications)

26 pages, 888 KB

Open AccessEditor’s ChoiceReview

Current Trends in Approaches to Prevent and Control Antimicrobial Resistance in Aquatic Veterinary Medicine

by Dongqing Zhao, Konrad Wojnarowski, Paulina Cholewińska and Dušan Palić

Pathogens 2025, 14(7), 681; https://doi.org/10.3390/pathogens14070681 - 10 Jul 2025

Cited by 3 | Viewed by 2936

Abstract

The growth of aquaculture production in recent years has revealed multiple challenges, including the rise of antimicrobial resistance (AMR) in aquatic animal production, which is currently attracting significant attention from multiple one-health stakeholders. While antibiotics have played a major role in the treatment [...] Read more.

The growth of aquaculture production in recent years has revealed multiple challenges, including the rise of antimicrobial resistance (AMR) in aquatic animal production, which is currently attracting significant attention from multiple one-health stakeholders. While antibiotics have played a major role in the treatment of bacterial infections for almost a century, a major consequence of their use is the increase in AMR, including the emergence of AMR in aquaculture. The AMR phenomenon creates a situation where antibiotic use in one system (e.g., aquaculture) may impact another system (e.g., terrestrial–human). Non-prudent use of antibiotics in aquaculture and animal farming increases the risk of AMR emergence, since bacteria harboring antibiotic resistance genes can cross between compartments such as wastewater or other effluents to aquatic environments, including intensive aquaculture. Transferable antimicrobial resistance gene (AMG) elements (plasmids, transposons, integrons, etc.) have already been detected in varying degrees from pathogenic bacteria that are often causing infections in farmed fish (Aeromonas, Vibrio, Streptococcus, Pseudomonas, Edwardsiella, etc.). This review of current veterinary approaches for the prevention and control of AMR emergence in aquaculture focuses on the feasibility of alternatives to antimicrobials and supplemental treatment applications during on-farm bacterial disease control and prevention. The use of vaccines, bacteriophages, biosurfactants, probiotics, bacteriocins, and antimicrobial peptides is discussed. Full article

► Show Figures

Figure 1

14 pages, 1293 KB

Open AccessEditor’s ChoiceArticle

Comprehensive Survey of PCV2 and PCV3 in Domestic Pigs and Wild Boars Across Portugal: Prevalence, Geographical Distribution and Genetic Diversity

by Bernardo Almeida, Margarida D. Duarte, Ana Duarte, Teresa Fagulha, Fernanda Ramos, Tiago Luís, Inês Caetano, Sílvia C. Barros, Fábio Abade dos Santos and Ana Margarida Henriques

Pathogens 2025, 14(7), 675; https://doi.org/10.3390/pathogens14070675 - 9 Jul 2025

Cited by 3 | Viewed by 1724

Abstract

Porcine circoviruses are significant pathogens that affect swine populations worldwide, with implications for animal health and productivity. While PCV2 is well-documented, particularly due to widespread vaccination programs, PCV3 is less understood, and its epidemiological impact is still under investigation. This study screened for [...] Read more.

Porcine circoviruses are significant pathogens that affect swine populations worldwide, with implications for animal health and productivity. While PCV2 is well-documented, particularly due to widespread vaccination programs, PCV3 is less understood, and its epidemiological impact is still under investigation. This study screened for PCV2 and PCV3 in pigs and wild boars across Portugal to assess their prevalence. Also, nucleotide sequence determination was performed to evaluate the genetic diversity of these viruses. Stool samples from 160 pigs belonging to different groups (quarantine, nursery, fattening and adult pigs), as well as organ samples from 120 hunted wild boars, were analyzed. Samples were collected from twelve of the eighteen mainland Portuguese districts with positive cases being detected in nine of them. Pigs had a lower prevalence of PCV2 (1.9%) than PCV3 (11.2%), but the opposite was true in wild boars (76.7% for PCV2 and 55.0% for PCV3). The lower PCV2 prevalence in pigs can be attributed to the PCV2 vaccination program implemented. Additionally, these viruses were significantly more prevalent in wild boars (90.8% were infected with at least one of the viruses) than in domestic pigs (only 12.5%). This significant difference highlights the impact of the controlled environment in pig farms on disease prevention in contrast to the higher exposure risks faced by wild boars in their natural habitat. Compared to a previous study from 2023, we observed a slight decrease in the percentage of positive cases for both PCV2 and PCV3. Phylogenetic analysis of sequences obtained by Sanger sequencing allowed us to conclude that the samples from domestic pigs belong to the PCV2a and PCV3c clades, in contrast to the PCV2-positive cases detected in domestic pigs in 2023 that were classified in the PCV2d genotype. Conversely, samples from wild boars belong to the PCV2d and PCV3a clades. These results reveal genotype differences between wild and domestic pigs and shifts from 2023 to 2024. Our findings provide some information about the circulation of these viruses and emphasize the importance of vaccination and continued monitoring for a deeper understanding of their epidemiology to mitigate potential risks to swine health and production. Full article

(This article belongs to the Special Issue Current Challenges in Veterinary Virology)

► Show Figures

Figure 1

15 pages, 1885 KB

Open AccessEditor’s ChoiceReview

Molecular Features of HPV-Independent Cervical Cancers

by Luca Giannella, Camilla Grelloni, Leonardo Natalini, Gianmarco Sartini, Mila Bordini, Giovanni Delli Carpini, Jacopo Di Giuseppe, Erica Dugo, Francesco Piva and Andrea Ciavattini

Pathogens 2025, 14(7), 668; https://doi.org/10.3390/pathogens14070668 - 8 Jul 2025

Cited by 6 | Viewed by 3394

Abstract

HPV-independent cervical cancers represent a small proportion of these types of cancers, predominantly glandular lesions. It should be noted that some cases may depend on diagnostic problems that lead to false negative cases. However, the most recent classifications distinguish cervical tumors into HPV-associated [...] Read more.

HPV-independent cervical cancers represent a small proportion of these types of cancers, predominantly glandular lesions. It should be noted that some cases may depend on diagnostic problems that lead to false negative cases. However, the most recent classifications distinguish cervical tumors into HPV-associated and HPV-independent cancers. HPV-negative cervical carcinomas (5–11% of all cases) mainly include rare adenocarcinomas (gastric, mesonephric, clear, serous, and endometrioid) and present distinct clinical and molecular features. These tumors usually affect older women and are diagnosed at more advanced stages than HPV-positive tumors, with an overall worse prognosis. This concerning and notably worse prognosis highlights the need for further research and understanding. Unlike HPV-positive carcinomas (which depend on the viral oncogenes E6/E7), HPV-independent tumors accumulate genomic mutations that activate oncogenes and inactivate suppressor genes. Therefore, a comprehensive overview of these aspects can be the key to a better understanding and developing personalized treatments. In the present review, the main mutated genes, the signaling pathways involved, the differences from HPV-positive tumors, the distinctive immunohistochemical markers, and the diagnostic and therapeutic implications are explored in depth. Full article

(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)

► Show Figures

Figure 1

9 pages, 789 KB

Open AccessEditor’s ChoiceArticle

Pharmacokinetics of Molnupiravir in Cats with Naturally Occurring Feline Infectious Peritonitis

by Petra Černá, Luke Wittenburg, Jennifer Hawley, McKenna Willis, Britta Siegenthaler and Michael R. Lappin

Pathogens 2025, 14(7), 666; https://doi.org/10.3390/pathogens14070666 - 7 Jul 2025

Cited by 3 | Viewed by 4503

Abstract

Antiviral drugs like EIDD-2801 (molnupiravir; MPV) have been successfully used in the treatment of feline infectious peritonitis (FIP). The previous study of the pharmacokinetics of MPV in healthy cats showed promise for its use and safety. The objective was to determine the pharmacokinetics [...] Read more.

Antiviral drugs like EIDD-2801 (molnupiravir; MPV) have been successfully used in the treatment of feline infectious peritonitis (FIP). The previous study of the pharmacokinetics of MPV in healthy cats showed promise for its use and safety. The objective was to determine the pharmacokinetics of molnupiravir in cats with naturally occurring FIP by measuring MPV and EIDD-193 (β-D-N4-hydroxycytidine; NHC) serum levels. Blood was collected from seven cats diagnosed with naturally occurring FIP treated at 1, 2, 4, 6 and 12 h post oral MPV administration and at 12 h post pill administration 7 days later. Serum concentrations of MPV and NHC were determined using a previously published high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method. The mean dose of MPV was 15.44 mg/kg (SD ± 1.82). The mean peak serum concentration of MPV (C_max) after a single PO dose of MPV was 38 ng/mL (SD ± 5). The mean peak serum concentration of NHC (C_max) after a single PO dose of MVP was 1551 ng/mL (SD ± 720). the time to reach NHC C_max (T_max) was 2.6 h (SD ± 1.4), and the NHC elimination half-life was 1.6 h (SD ± 1.1). Minimal drug accumulation was seen in trough concentrations following twice-daily dosing for 7 days. The low MPV levels may be explained by fast conversion to its active metabolite NHC. The mean NHC concentrations at all time points were at least 4 times the reported in vitro IC₅₀ for feline coronavirus strains and twice-daily dosing for seven days did not lead to drug accumulation within the serum. The results support the use of MPV in the treatment of FIP, and if therapeutic drug monitoring is to be performed, NHC should be measured. Full article

(This article belongs to the Special Issue Feline Coronavirus Infections)

► Show Figures

Figure 1

34 pages, 981 KB

Open AccessEditor’s ChoiceReview

Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review

by Chloë Hanssens and Jolien Van Cleemput

Pathogens 2025, 14(7), 654; https://doi.org/10.3390/pathogens14070654 - 1 Jul 2025

Viewed by 5646

Abstract

Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to [...] Read more.

Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to a broad spectrum of clinical manifestations, ranging from mild symptoms to severe disease, particularly in immunocompromised individuals. Clustered regularly interspaced palindromic repeats (CRISPR)-based therapy is an interesting alternative to current antiviral drugs, which fail to cure latent infections and are increasingly challenged by viral resistance. Objective: This scoping review aimed to summarize the current state of CRISPR-based antiviral strategies against herpesvirus infections, highlighting the underlying mechanisms, study design and outcomes, and challenges for clinical implementation. Design: A literature search was conducted in the databases PubMed and Web of Science, using both a general and an individual approach for each herpesvirus. Results: This scoping review identified five main mechanisms of CRISPR-based antiviral therapy against herpesvirus infections in vitro and/or in vivo. First, CRISPR systems can inhibit the active lytic replication cycle upon targeting viral lytic genes or host genes. Second, CRISPR technologies can remove latent viral genomes from infected cells by targeting viral genes essential for latency maintenance or destabilizing the viral genome. Third, reactivation of multiple latent herpesvirus infections can be inhibited by CRISPR-Cas-mediated editing of lytic viral genes, preventing a flare-up of clinical symptoms and reducing the risk of viral transmission. Fourth, CRISPR systems can purposefully induce viral reactivation to enhance recognition by the host immune system or improve the efficacy of existing antiviral therapies. Fifth, CRISPR technology can be applied to develop or enhance the efficiency of cellular immunotherapy. Conclusions: Multiple studies demonstrate the potential of CRISPR-based antiviral strategies to target herpesvirus infections through various mechanisms in vitro and in vivo. However, aspects regarding the delivery and biosafety of CRISPR systems, along with the time window for treatment, require further investigation before broad clinical implementation can be realized. Full article

(This article belongs to the Special Issue Herpesvirus Latency and Reactivation)

► Show Figures

Figure 1

33 pages, 5228 KB

Open AccessEditor’s ChoiceReview

Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?

by Hannah Preston, Rowan Casey, Elizabeth Ferris, Lauren Kerr-Jones, Lauren Jones, Farah Latif, Mathew Clement, Rebecca J. Aicheler, Eddie C. Y. Wang, Richard J. Stanton and Ceri A. Fielding

Pathogens 2025, 14(7), 629; https://doi.org/10.3390/pathogens14070629 - 24 Jun 2025

Cited by 5 | Viewed by 3551

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous member of the herpesvirus family, of significant clinical importance, and highly adapted to its host, resulting from millions of years of co-evolution. As a result, the virus systematically subverts almost all aspects of antiviral immune defence to [...] Read more.

Human cytomegalovirus (HCMV) is a ubiquitous member of the herpesvirus family, of significant clinical importance, and highly adapted to its host, resulting from millions of years of co-evolution. As a result, the virus systematically subverts almost all aspects of antiviral immune defence to successfully establish a lifelong persistent infection, and in the process, dramatically reshapes the phenotype and function of host immunity to both HCMV and other diseases. Natural killer (NK) cells are a critical component of successful herpesvirus control. Here, we discuss their role in modulating HCMV disease and the multitude of ways that HCMV has evolved to prevent and manipulate this process. We also consider how antibody-dependent cellular cytotoxicity by NK cells directed against HCMV might overcome NK immune evasion mechanisms and be useful therapeutically. Full article

(This article belongs to the Special Issue Understanding Human Cytomegalovirus Pathogenesis: Evidence from the Clinic and Laboratory Models)

► Show Figures

Figure 1

20 pages, 600 KB

Open AccessEditor’s ChoiceReview

Challenges and Prospects for Eradication of Helicobacter pylori: Targeting Virulence Factors, Metabolism, and Vaccine Innovation

by Adrian Bakiera, Anita Solarz, Marika Kowalczyk, Halina Cichoż-Lach and Izabela Korona-Głowniak

Pathogens 2025, 14(7), 619; https://doi.org/10.3390/pathogens14070619 - 21 Jun 2025

Cited by 4 | Viewed by 4994

Abstract

Helicobacter pylori is a Gram-negative bacterium that infects almost half of the global population and is linked to gastric conditions like peptic ulcers and gastric cancer, as well as other diseases such as neurological disorders, cardiovascular problems, and iron deficiency anemia. Its survival [...] Read more.

Helicobacter pylori is a Gram-negative bacterium that infects almost half of the global population and is linked to gastric conditions like peptic ulcers and gastric cancer, as well as other diseases such as neurological disorders, cardiovascular problems, and iron deficiency anemia. Its survival in the acidic stomach environment is due to virulence factors like urease, flagella, and adhesion proteins (BabA, SabA). Current treatments involve a combination of antibiotics (clarithromycin, metronidazole, amoxicillin, tetracycline) and proton pump inhibitors, but increasing antibiotic resistance, especially to clarithromycin and metronidazole, poses a major challenge. Resistance mechanisms include mutations in drug targets, efflux pump overexpression, and enzymatic degradation of antibiotics. This has prompted exploration of alternative therapies targeting bacterial processes like urease activity, biofilm formation, and metabolic pathways (energy production, amino acid synthesis, iron acquisition). Natural compounds, such as chitosan and plant extracts, show promise in combating H. pylori growth and virulence. Vaccine development is also ongoing, with DNA vaccines showing potential for broad immune responses. However, no vaccine is yet close to widespread clinical use. Full article

(This article belongs to the Section Bacterial Pathogens)

► Show Figures

Figure 1

13 pages, 1514 KB

Open AccessEditor’s ChoiceArticle

Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses

by Kaixin Li, Misa Katayama, Ayano Ichikawa, Hiromichi Matsugo, Yuta Wakabayashi, Akiko Takenaka-Uema, Wataru Sekine, Taisuke Horimoto and Shin Murakami

Pathogens 2025, 14(6), 605; https://doi.org/10.3390/pathogens14060605 - 19 Jun 2025

Viewed by 1861

Abstract

Merbecovirus, a subgenus of Betacoronavirus, includes MERS-CoV and multiple bat-derived viruses with zoonotic potential. Given the unpredictable emergence of these viruses and their genetic diversity, development of broad-spectrum diagnostic tools is expected. In this study, we established a sandwich ELISA targeting [...] Read more.

Merbecovirus, a subgenus of Betacoronavirus, includes MERS-CoV and multiple bat-derived viruses with zoonotic potential. Given the unpredictable emergence of these viruses and their genetic diversity, development of broad-spectrum diagnostic tools is expected. In this study, we established a sandwich ELISA targeting the nucleocapsid (N) protein of merbecoviruses. We generated monoclonal antibodies (mAbs) using recombinant N protein of a bat merbecovirus, VsCoV-1, and selected cross-reactive clones for other merbecoviruses. Three mAbs showed strong reactivities with multiple merbecoviruses but not with SARS-CoV-2 or endemic human coronaviruses. Pairwise ELISA screening identified 1A8/10H6 mAbs as the optimal combination for detection of N protein from six merbecoviruses—VsCoV-1, EjCoV-3, MERS-CoV, NeoCoV, HKU4, and HKU5—with limits of detection (LODs) below 7.81 ng/mL, including 1.25 ng/mL for VsCoV-1. Infectious bat merbecovirus EjCoV-3 was detected at 1.3 × 10³ PFU/mL. No cross-reactivity was observed with non-merbecoviruses, indicating its high specificity. This sandwich ELISA offers a rapid, reproducible, and cost-effective diagnostic platform with potential for high-throughput screening and automation. Moreover, its design is amenable to adaptation into point-of-care formats such as lateral flow assays, highlighting its value for field-based surveillance and pandemic preparedness. Full article

(This article belongs to the Special Issue The Epidemiology and Diagnosis of Acute Respiratory Infections)

► Show Figures

Figure 1

20 pages, 1074 KB

Open AccessEditor’s ChoiceArticle

The Epidemiology of Coccidioidomycosis (Valley fever) and the Disease Ecology of Coccidioides spp. in New Mexico (2006–2023)

by Paris S. Salazar-Hamm, Sarah Shrum Davis, Jovani Catalán-Dibene, Adriana L. Romero-Olivares, Karen Edge, Andrew W. Bartlow, Donald O. Natvig and Morgan E. Gorris

Pathogens 2025, 14(6), 607; https://doi.org/10.3390/pathogens14060607 - 19 Jun 2025

Cited by 1 | Viewed by 3318

Abstract

Coccidioidomycosis (Valley fever), caused by Coccidioides spp., is a fungal infection endemic to semi-arid regions of the Americas. Despite 80 years of disease recognition in New Mexico, there is limited disease awareness. We incorporated clinical, epidemiological, and ecological datasets to summarize the knowledge [...] Read more.

Coccidioidomycosis (Valley fever), caused by Coccidioides spp., is a fungal infection endemic to semi-arid regions of the Americas. Despite 80 years of disease recognition in New Mexico, there is limited disease awareness. We incorporated clinical, epidemiological, and ecological datasets to summarize the knowledge of Valley fever in New Mexico. We analyzed 1541 human cases from 2006 to 2023. On average, 86 cases were reported each year (4.1 cases per 100,000 population per year). The highest levels of incidence were in southwestern New Mexico. American Indian or Alaska Natives in New Mexico had a 1.9 times higher incidence rate of coccidioidomycosis than White people, and among age groups, older populations in New Mexico had the highest incidence rates. We analyzed 300 soil samples near Las Cruces, New Mexico, for the presence of Coccidioides and reported the first known positive soil samples collected from the state, the majority of which were from grassland-dominated sites and from animal burrows. Sequence analyses in clinical specimens, wild animals, and soil samples confirmed that Coccidioides posadasii is the main causative species of coccidioidomycosis in New Mexico. Environmental surveillance validated that locally acquired infections could occur in, but are not limited to, Catron, Doña Ana, Sierra, and Socorro Counties. Full article

(This article belongs to the Special Issue An Update on Fungal Infections)

► Show Figures

Figure 1

29 pages, 2576 KB

Open AccessEditor’s ChoiceReview

A Comprehensive Review of the Mechanisms of Human Q Fever: Pathogenesis and Pathophysiology

by José-Luis Pérez-Arellano, Jose Curbelo and Cristina Carranza-Rodriguez

Pathogens 2025, 14(6), 589; https://doi.org/10.3390/pathogens14060589 - 14 Jun 2025

Cited by 5 | Viewed by 4187

Abstract

Coxiella burnetii infection has a worldwide distribution, although the incidence and clinical manifestations vary between and within countries. There are the following four basic forms: asymptomatic infection, acute Q fever, chronic Q fever, and post-Q fever fatigue syndrome. The aim of this review [...] Read more.

Coxiella burnetii infection has a worldwide distribution, although the incidence and clinical manifestations vary between and within countries. There are the following four basic forms: asymptomatic infection, acute Q fever, chronic Q fever, and post-Q fever fatigue syndrome. The aim of this review is to provide a comprehensive overview of the important aspects of its pathogenesis and pathophysiology. First, we provide a brief update of the taxonomic aspects, basic structures, and genotypes of C. burnetii necessary for the proper interpretation of the following sections. Routes of infection, different stages of pathogenesis (respiratory entry of C. burnetii; penetration into alveolar macrophages, life cycle, and effects; systemic dissemination), and innate, acquired humoral and cell-mediated immune responses in different forms of infection are described in detail. The pathophysiology and clinical manifestations of Q fever, such as the main mechanisms of injury, in isolation and in combination, are reviewed. The clinical and biological manifestations of the two main forms of Q fever (acute and chronic) are outlined, with a brief definition and mention of the mechanisms of post-Q fever fatigue syndrome. Full article

(This article belongs to the Section Bacterial Pathogens)

► Show Figures

Figure 1

60 pages, 6483 KB

Open AccessEditor’s ChoiceReview

The Challenge of Lyssavirus Infections in Domestic and Other Animals: A Mix of Virological Confusion, Consternation, Chagrin, and Curiosity

by Charles E. Rupprecht, Aniruddha V. Belsare, Florence Cliquet, Philip P. Mshelbwala, Janine F. R. Seetahal and Vaughn V. Wicker

Pathogens 2025, 14(6), 586; https://doi.org/10.3390/pathogens14060586 - 13 Jun 2025

Cited by 1 | Viewed by 7808

Abstract

Lyssaviruses are RNA viruses in the Family Rhabdoviridae, Genus Lyssavirus. They represent the causative agents of acute, progressive encephalitis, known historically as rabies. Regardless of specific etiology, their collective viral morphology, biochemistry, pathobiology, associated clinical signs, diagnosis, epizootiology, and management are essentially [...] Read more.

Lyssaviruses are RNA viruses in the Family Rhabdoviridae, Genus Lyssavirus. They represent the causative agents of acute, progressive encephalitis, known historically as rabies. Regardless of specific etiology, their collective viral morphology, biochemistry, pathobiology, associated clinical signs, diagnosis, epizootiology, and management are essentially the same. Despite centuries of clinical recognition, these quintessential neurotropic agents remain significant pathogens today, with substantive consequences to agriculture, public health, and conservation biology. Notably, the singular morbidity caused by lyssaviruses is incurable and constitutes the highest case fatality of any viral disease. All warm-blooded vertebrates are believed to be susceptible. The dog is the only domestic animal that serves as a reservoir, vector, and victim. In contrast, felids are effective vectors, but not reservoirs. All other rabid domestic species, such as livestock, constitute spillover infections, as a bellwether to local lyssavirus activity. Frequently, professional confusion abounds among the veterinary community, because although the viral species Lyssavirus rabies is inarguably the best-known representative in the Genus, at least 20 other recognized or putative members of this monophyletic group are known. Frequently, this is simply overlooked. Moreover, often the ‘taxonomic etiology’ (i.e., ‘Lyssavirus x’) is mistakenly referenced in a biopolitcal context, instead of the obvious clinical illness (i.e., ‘rabies’). Global consternation persists, if localities believe they are ‘disease-free’, when documented lyssaviruses circulate or laboratory-based surveillance is inadequate to support such claims. Understandably, professional chagrin develops when individuals mistake the epidemiological terminology of control, prevention, elimination, etc. Management is not simple, given that the only licensed veterinary and human vaccines are against rabies virus, sensu lato. There are no adequate antiviral drugs for any lyssaviruses or cross-reactive biologics developed against more distantly related viral members. While representative taxa among the mammalian Orders Chiroptera, Carnivora, and Primates exemplify the major global reservoirs, which mammalian species are responsible for the perpetuation of other lyssaviruses remains a seemingly academic curiosity. This zoonosis is neglected. Clearly, with such underlying characteristics as a fundamental ‘disease of nature’, rabies, unlike smallpox and rinderpest, is not a candidate for eradication. With the worldwide zeal to drive human fatalities from canine rabies viruses to zero by the rapidly approaching year 2030, enhanced surveillance and greater introspection of the poorly appreciated burden posed by rabies virus and diverse other lyssaviruses may manifest as an epidemiological luxury to the overall global program of the future. Full article

(This article belongs to the Special Issue Current Challenges in Veterinary Virology)

► Show Figures

Figure 1

16 pages, 1357 KB

Open AccessEditor’s ChoiceArticle

EmsB Microsatellite Analysis of Echinococcus multilocularis Specimens Isolated from Belgian Patients with Alveolar Echinococcosis and from Animal Hosts

by Sabrina Egrek, Jenny Knapp, Rosalie Sacheli, Khalid El Moussaoui, Philippe Léonard, Eva Larranaga Lapique, Laurence Millon, Sara Engelskirchen, Olivier Detry, Annick Linden and Marie-Pierre Hayette

Pathogens 2025, 14(6), 584; https://doi.org/10.3390/pathogens14060584 - 12 Jun 2025

Viewed by 1238

Abstract

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E. multilocularis), is a severe parasitic zoonosis that is potentially fatal for humans. The parasite is primarily transmitted by wildlife, with red foxes acting as definitive hosts and rodents as intermediate hosts, while humans [...] Read more.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E. multilocularis), is a severe parasitic zoonosis that is potentially fatal for humans. The parasite is primarily transmitted by wildlife, with red foxes acting as definitive hosts and rodents as intermediate hosts, while humans can become accidental but dead-end hosts. The aim of this study is to use EmsB typing on E. multilocularis isolates from human AE cases and local animals such as foxes and rodents. In this study, retrospective EmsB typing was performed on 39 samples, including 11 tissue samples from 10 patients, 18 fecal swabs from foxes, and 10 tissue samples from rodents. A dendrogram was created to determine the EmsB profiles present. The results showed that all the rodent samples were associated with the EmsB P1 profile (10/10), while the human and fox samples shared the EmsB profile P1 (5/11 humans and 8/18 foxes), a profile near P4 (2/11 humans and 3 foxes), and a profile near P8 (1/11 humans and 1/18 foxes). The study demonstrates that the same EmsB profiles circulate among humans and animals, confirming that wildlife reservoirs play a key role in transmission. Full article

(This article belongs to the Section Parasitic Pathogens)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI