Pathogens

14 pages, 1234 KB

Open AccessEditor’s ChoiceArticle

Staphylococci: What Has Changed in the Antibiotic Resistance Profile in the Last Decade—Analysis of Strains Isolated from Hospitalised Patients

by Alessio Facciolà, Antonio Laganà, Maria Eufemia Gioffrè, Alessandro Morabito, Domenico Chiera, Marco Ferlazzo and Pasqualina Laganà

Pathogens 2025, 14(12), 1289; https://doi.org/10.3390/pathogens14121289 - 15 Dec 2025

Viewed by 798

Abstract

Antibiotic resistance can be considered one of the major bacterial pathogenesis factors, and its increase is an important public health concern. Among resistant bacteria, staphylococci can express high levels of resistance, representing some of the most common human pathogens that are important causes [...] Read more.

Antibiotic resistance can be considered one of the major bacterial pathogenesis factors, and its increase is an important public health concern. Among resistant bacteria, staphylococci can express high levels of resistance, representing some of the most common human pathogens that are important causes of infection at any level. This paper aims to assess the burden of staphylococcal infections, in light of the growing phenomenon of antibiotic resistance, in a high-risk hospital setting. We carried out a cross-sectional study on data obtained from clinical specimens from an Italian healthcare facility particularly specialised in orthopaedics and traumatology. Specifically, we evaluated the trends in the Staphylococcus spp. detection rates and antibiotic resistance in the ten-year period of 2012–2024. The number of specimens increased over time but remarkably decreased during the COVID-19 pandemic. Despite this, the detection rate of Staphylococcus spp. remained quite constant, confirming the common circulation of these pathogens in such nosocomial environments. Antibiotic resistance concomitantly decreased, but a novel increase was found in recent years. Our findings highlight the importance of continuous monitoring of the antibiotic resistance rates of staphylococci due to the importance of these pathogens in human pathology and their ability to cause life-threatening antibiotic-resistant infections. Full article

(This article belongs to the Collection New Insights into Bacterial Pathogenesis)

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17 pages, 713 KB

Open AccessEditor’s ChoiceArticle

The Use of Point-of-Care Tests and Multiplex PCR Tests in the Pediatric Emergency Department Reduces Antibiotic Prescription in Patients with Febrile Acute Respiratory Infections

by Luca Pierantoni, Arianna Dondi, Liliana Gabrielli, Valentina Lasala, Laura Andreozzi, Laura Bruni, Fiorentina Guida, Eleonora Battelli, Giulia Piccirilli, Ilaria Corsini, Tiziana Lazzarotto, Marcello Lanari and Daniele Zama

Pathogens 2025, 14(12), 1284; https://doi.org/10.3390/pathogens14121284 - 13 Dec 2025

Cited by 2 | Viewed by 1109

Abstract

Background: Acute Respiratory Infections are a common reason for Pediatric Emergency Department (PED) visits. Differentiating bacterial and viral infections may be challenging and might result in incorrect antibiotic prescriptions and exacerbation of antimicrobial resistance. This study evaluated the impact of new diagnostic tests [...] Read more.

Background: Acute Respiratory Infections are a common reason for Pediatric Emergency Department (PED) visits. Differentiating bacterial and viral infections may be challenging and might result in incorrect antibiotic prescriptions and exacerbation of antimicrobial resistance. This study evaluated the impact of new diagnostic tests in PED. Methods: A retrospective cohort of 4882 acute febrile respiratory infection cases presenting to the PED was analyzed, comparing two periods: Period 1 (October 2016–March 2017, n = 2181) and Period 2 (October 2023–March 2024, n = 2701). During Period 1, Group A Streptococcus and Respiratory Syncytial Virus rapid antigen detection tests were available. During Period 2, new point-of-care tests (POCTs), including rapid C-reactive protein and rapid antigen detection for Influenza A, Influenza B, and SARS-CoV-2, and a multiplex PCR nasal swab, were introduced. Results: In Period 2, antibiotic prescriptions decreased by 28.4%, along with a reduction in broad-spectrum antibiotic use. A significant correlation was observed between reduced antibiotic prescription and the use of new POCTs and multiplex PCR tests. Performance of blood tests and chest radiographs also decreased. Conclusions: Implementing novel diagnostic tests in PED helps clinicians select more appropriate management options with an impact on reduced stress and radiation exposure and antibiotic prescription. Full article

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12 pages, 2309 KB

Open AccessEditor’s ChoiceArticle

Complete Genome Sequences of Human Japanese Encephalitis Virus Genotype V Isolates in Korea Reveal Genotype-Specific Amino Acid Signatures

by Seung-Rye Cho, Ye-Ji Lee, Myung Guk Han and Heui Man Kim

Pathogens 2025, 14(12), 1279; https://doi.org/10.3390/pathogens14121279 - 12 Dec 2025

Cited by 2 | Viewed by 986

Abstract

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus causing severe neurological disease across Asia, and genotype V (GV) is now predominant in Korea. Despite frequent detection of GV in mosquitoes, human-derived complete genome data remain scarce. To elucidate the molecular and antigenic [...] Read more.

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus causing severe neurological disease across Asia, and genotype V (GV) is now predominant in Korea. Despite frequent detection of GV in mosquitoes, human-derived complete genome data remain scarce. To elucidate the molecular and antigenic characteristics of human GV infections, cerebrospinal fluid samples from unvaccinated patients positive for JEV RNA during 2018–2023 were subjected to virus isolation in LLC-MK2 cells (rhesus monkey kidney-derived epithelial cell line). Three human GV isolates (K18P80, K23P84, K23P88) were successfully obtained and their complete open reading frames (~10.3 kb) sequenced. Phylogenetic analysis with representative JEV strains (GI–GV) revealed that these isolates form a distinct lineage, clustering into two domestic clades (Clade I and II), suggesting endemic circulation and local evolution in Korea. Sequence identities with GIII-based vaccine strains were low (79% nucleotide, 91.1% amino acid), with notable divergence in nonstructural regions. Three consistent E protein substitutions (Q52E, S156T, D292E) near antigenic epitopes indicate possible immune escape. Additional clade-defining substitutions in NS3 (L31F) and NS5 (K269R, M330I) were shared with mosquito isolates, supporting human–vector molecular continuity. These findings provide fundamental genomic evidence of human JEV GV in Korea and highlight the need for genotype-specific surveillance and next-generation vaccine evaluation. Full article

(This article belongs to the Topic Genetic, Environmental, and Climatic Drivers of Emerging Arboviruses and Public Health Implications)

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17 pages, 2713 KB

Open AccessEditor’s ChoiceArticle

Potential Use of Biosensors for the Rapid and Specific Isolation of Listeria monocytogenes from Ready-to-Eat (RTE) Foods

by McCoy Williams, Rawah Faraj, Rejoice Nyarku, Savannah Simon, Kingsley E. Bentum, Ahmed Ghazy, Yilkal Woube, Temesgen Samuel, Evangelyn Alocija and Woubit Abebe

Pathogens 2025, 14(12), 1280; https://doi.org/10.3390/pathogens14121280 - 12 Dec 2025

Cited by 1 | Viewed by 965

Abstract

Listeria monocytogenes is a major foodborne pathogen associated with increasing global public health concern due to numerous outbreaks. Rapid pathogen detection is critical for reducing both the incidence and severity of foodborne illnesses. Recent advances in nanotechnology are transforming analytical methods, particularly for [...] Read more.

Listeria monocytogenes is a major foodborne pathogen associated with increasing global public health concern due to numerous outbreaks. Rapid pathogen detection is critical for reducing both the incidence and severity of foodborne illnesses. Recent advances in nanotechnology are transforming analytical methods, particularly for detecting foodborne pathogens. Magnetic nanoparticles (MNPs) and gold nanoparticles (GNPs) are among the most widely used nanomaterials in this field. This study investigated the potential use of MNPs and GNPs for the rapid and specific isolation of L. monocytogenes from fresh salad, deli meat, and frozen vegetables. L. monocytogenes (ATCC 19117) served as the model organism for biosensing and target capture. Results showed that the limits of detection (LoDs) for the GNP-based plasmonic/colorimetric biosensor and the MNP-based biosensor were 2.5 ng/µL DNA and 1.5 CFU/mL, respectively. Both GNPs and MNPs specifically detected L. monocytogenes even in the presence of closely related pathogens. Integration of MNPs and GNPs significantly enhanced the sensitivity of L. monocytogenes detection. Within one hour, naturally contaminated pre-packaged salad samples demonstrated clear evidence of effective direct capture by MNPs and specific identification by GNPs. This combined approach enables rapid and accurate on-site detection of L. monocytogenes, facilitating timely intervention and reducing the risk of contaminated foods reaching consumers. Full article

(This article belongs to the Section Bacterial Pathogens)

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19 pages, 961 KB

Open AccessEditor’s ChoiceArticle

Prevalence of ESBL-Producing Escherichia coli on Neck Skin in Slaughtered Broilers Raised on Conventional, Antibiotic-Free, and Organic Farms

by Giulia Dilio, Francesca Blasi, Silvia Tofani, Elisa Albini, Serenella Orsini, Marcella Ciullo, Francesca Romana Massacci, Michele Pesciaroli, Giovanni Pezzotti and Chiara Francesca Magistrali

Pathogens 2025, 14(12), 1265; https://doi.org/10.3390/pathogens14121265 - 10 Dec 2025

Cited by 1 | Viewed by 1257

Abstract

Antimicrobial resistance (AMR) among commensal Escherichia coli from poultry is a growing concern for food safety and public health. This study investigated AMR patterns in E. coli isolated from broiler neck skin at slaughter, comparing organic, antibiotic-free (ATB-free), and conventional production systems. A [...] Read more.

Antimicrobial resistance (AMR) among commensal Escherichia coli from poultry is a growing concern for food safety and public health. This study investigated AMR patterns in E. coli isolated from broiler neck skin at slaughter, comparing organic, antibiotic-free (ATB-free), and conventional production systems. A total of 375 samples were collected from two Italian slaughterhouses and tested by broth microdilution following EU protocols. E. coli was recovered from 358 samples, and 37.9% were presumptively positive for ESBL/AmpC-producing strains. Conventional broilers showed the highest resistance to ampicillin (73.8%), sulfonamides (72.5%), and fluoroquinolones (nalidixic acid, 62.5%; ciprofloxacin, 67.5%), while organic and ATB-free systems showed significantly lower levels. Intermediate resistance occurred for trimethoprim (21.4–47.9%) and tetracycline (36–54%), and low prevalence (<10%) was found for gentamicin, tigecycline, and third-generation cephalosporins. No relevant resistance was detected to colistin or carbapenems (≤1.2%). Total E. coli counts did not differ among systems, suggesting differences in resistant strain proportions rather than bacterial load. ATB-free flocks processed after conventional batches displayed higher resistance, indicating possible cross-contamination during slaughter. These results highlight the influence of farming practices and slaughterhouse hygiene on AMR dissemination, underscoring the need for integrated farm-to-slaughter control strategies. Full article

(This article belongs to the Special Issue Challenges of Multidrug-Resistant Bacteria and Drug Development of Antibacterials)

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17 pages, 1972 KB

Open AccessEditor’s ChoiceArticle

Leishmaniavirus Type 1 Enhances In Vitro Infectivity and Modulates the Immune Response to Leishmania (Viannia) Isolates

by Armando A. Bonilla Fong, Vanessa J. Pineda, José E. Calzada, Marcia Dalastra Laurenti, Luiz Felipe Domingues Passero, Davis Beltran, Luis Fernando Chaves, Azael Saldaña and Kadir González

Pathogens 2025, 14(12), 1263; https://doi.org/10.3390/pathogens14121263 - 10 Dec 2025

Cited by 2 | Viewed by 712

Abstract

Leishmania RNA virus 1 (LRV-1) is a double-stranded RNA virus identified in several Leishmania spp. LRV-1 has been associated with increased disease severity and therapeutic failure in cutaneous leishmaniasis (CL). Although LRV-1 has been reported in the Americas, its influence on [...] Read more.

Leishmania RNA virus 1 (LRV-1) is a double-stranded RNA virus identified in several Leishmania spp. LRV-1 has been associated with increased disease severity and therapeutic failure in cutaneous leishmaniasis (CL). Although LRV-1 has been reported in the Americas, its influence on parasite infectivity and host immune responses remains poorly characterized in Panamanian isolates. In this study, we investigate the in vitro infectivity and immunomodulatory effects of LRV-1-positive (LRV-1⁺) versus LRV-1-negative (LRV-1⁻) isolates of Leishmania (Viannia), including clinical strains of L. (V.) panamensis and L. (V.) guyanensis. A total of 21 isolates (nine LRV-1⁺, nine LRV-1⁻, and three reference strains) were used to infect human U937 macrophages. The infectivity index (II) was measured at 24, 48, and 72 h post-infection. Cytokine levels of TNF-α, IFN-γ, IL-4, IL-6, IL-10, and IL-17 were quantified by flow cytometry, and IL-1β by ELISA at 24 and 48 h. LRV-1⁺ isolates exhibited significantly higher infectivity at 48 h (mean II = 1386.2) and 72 h (mean II = 1316.8) compared to LRV-1⁻ isolates (mean II = 714.4 and 571.0, respectively; p < 0.001). Two L. (V.) panamensis LRV-1⁺ isolates associated with complicated CL cases displayed the highest II values. Cytokine analysis revealed that LRV-1⁺ isolates induced elevated TNF-α (p < 0.01) and IL-1β (p < 0.001), along with reduced IFN-γ (p < 0.01), while no significant differences were observed for IL-4, IL-6, IL-10, or IL-17. These findings indicate that LRV-1 enhances parasite infectivity and promotes a pro-inflammatory cytokine profile, which may contribute to disease persistence and treatment failure. Full article

(This article belongs to the Special Issue Leishmaniases: From Clinical Presentation, to Pathogenesis and Basic Science)

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21 pages, 3344 KB

Open AccessEditor’s ChoiceArticle

Thermal Inactivation of Multiple Veterinary-Relevant Viruses: Effects of Environmental Conditions, Surface Type, and Organic Matrix

by Isac Junior Roman, Ingryd Merchioratto, Renata Nobre da Fonseca, Mayara Fernanda Maggioli and Fernando Vicosa Bauermann

Pathogens 2025, 14(12), 1243; https://doi.org/10.3390/pathogens14121243 - 5 Dec 2025

Viewed by 1179

Abstract

Heat is widely used to decontaminate livestock environments, yet performance varies with virus, surface, moisture, and organic load. We evaluated the effects of temperature (50, 60, 70 °C) and exposure time on the viability of 10 veterinary-relevant viruses (or surrogates) placed on four [...] Read more.

Heat is widely used to decontaminate livestock environments, yet performance varies with virus, surface, moisture, and organic load. We evaluated the effects of temperature (50, 60, 70 °C) and exposure time on the viability of 10 veterinary-relevant viruses (or surrogates) placed on four nonporous surfaces (plastic, rubber, aluminum, stainless steel) under dry or wet conditions, and in organic matrices (blood, wheat straw, complete feed). Infectivity was quantified by TCID₅₀ using independent duplicate experiments with duplicate titrations. Moist heat consistently outperformed dry heat: at 60–70 °C, all enveloped viruses, and most non-enveloped viruses were inactivated on surfaces within 5 min, while porcine parvovirus (PPV) remained the outlier, requiring ≥60 min. In contrast, dry heat allowed several viruses to persist for 24 h at 70 °C, underscoring that temperature alone is an unreliable predictor of rapid decontamination in the absence of humidity. Organic matrices modulated outcomes in a substrate- and virus-dependent manner, with some combinations accelerating inactivation and others prolonging survival to ≥180 min at ≥60 °C. These findings support matrix-aware, heat-assisted protocols for facilities and transport (e.g., 70 °C for ≥10 min under high humidity for most enveloped viruses), while recognizing exceptions such as PPV. The data provide actionable parameters to optimize thermo-assisted decontamination in veterinary systems. Full article

(This article belongs to the Section Viral Pathogens)

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17 pages, 3547 KB

Open AccessEditor’s ChoiceArticle

The Canine Hookworm Ancylostoma Caninum: First Confirmed Evidence in a Dog in Central Europe: Epidemiological Relevance or Coincidence?

by Michaela Liptáková, Andrea Schreiberová, Zuzana Cellengová, Viktória Kožárová and Gabriela Štrkolcová

Pathogens 2025, 14(12), 1241; https://doi.org/10.3390/pathogens14121241 - 4 Dec 2025

Viewed by 2413

Abstract

Canine hookworms represent some of the most globally prevalent parasitic nematodes affecting dogs and pose a significant zoonotic risk to humans, in whom they can induce cutaneous larva migrans. Infection with these parasites may lead to blood loss, anaemia, and, in severe cases, [...] Read more.

Canine hookworms represent some of the most globally prevalent parasitic nematodes affecting dogs and pose a significant zoonotic risk to humans, in whom they can induce cutaneous larva migrans. Infection with these parasites may lead to blood loss, anaemia, and, in severe cases, mortality—particularly in young puppies. The present study reports a confirmed case of Ancylostoma caninum infection in a 15-month-old dog in the Slovak Republic. The infected dog presented with severe, persistent diarrhoea, and haematological examination revealed a decrease in erythrocyte and haemoglobin levels, as well as mild eosinophilia. Coprological examination confirmed the presence of nematodes belonging to the family of Ancylostomatidae. Following the initiation of anthelmintic therapy, adult individuals were recovered from the faeces. Based on distinct morphological characteristics, the parasites were presumptively attributed to the species A. caninum. Subsequent molecular analysis of the mitochondrial cytochrome c oxidase subunit 1 gene (COX1) and the ribosomal ITS regions definitively confirmed the species A. caninum. Our findings confirm that this is the first molecularly confirmed case of this species in Central Europe. This hookworm is predominantly found in warm and humid climatic regions. Its recent detection in Slovakia, a country characterised by a temperate climate, may suggest a northward expansion of its geographic range, potentially facilitated by ongoing climatic shifts associated with global climate change. Full article

(This article belongs to the Special Issue Updates on Zoonotic Parasites)

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13 pages, 1245 KB

Open AccessEditor’s ChoiceArticle

Prevalence of Borrelia afzelii and Borrelia garinii Genospecies in Ixodes ricinus Ticks Collected from Three Regions in Bulgaria

by Iskren Stanilov, Alexander Blazhev, Borislava Chakarova and Spaska Stanilova

Pathogens 2025, 14(12), 1240; https://doi.org/10.3390/pathogens14121240 - 4 Dec 2025

Viewed by 928

Abstract

The tick species Ixodes ricinus is the most widely distributed throughout Europe and serves as the primary vector for the spirochete Borrelia burgdorferi sensu lato (s.l.), which is responsible for Lyme borreliosis. The present study evaluated the prevalence of B. burgdorferi (s.l.) in [...] Read more.

The tick species Ixodes ricinus is the most widely distributed throughout Europe and serves as the primary vector for the spirochete Borrelia burgdorferi sensu lato (s.l.), which is responsible for Lyme borreliosis. The present study evaluated the prevalence of B. burgdorferi (s.l.) in I. ricinus ticks using nPCR amplification. Ticks were collected from three geographical regions in Bulgaria: the Black Sea Coast in the east, the Pleven region in the north, and the Stara Zagora region in the central south. This study focused on urban and peri-urban areas, including heavily traveled trails in parks. The results indicated statistically significant differences in infection rates, with the highest percentage of infected ticks found in Pleven (52.34%), followed by Stara Zagora (35.46%) and the lowest on the Black Sea Coast (23.08%). Furthermore, we conducted genospecies molecular identification of B. afzelii and B. garinii by PCR amplification of genospecies-specific nucleotide sequences in the 16S rRNA gene. The lowest prevalence of B. afzelii was recorded in Stara Zagora at 10.64%, followed by the Black Sea region at 12.5%, while the statistically highest frequency was observed in Pleven at 21.03%. The prevalence of B. garinii among the total number of I. ricinus ticks was greatest in Pleven at 15.89%, followed by the Black Sea region at 8.65%, and the lowest in the Stara Zagora region at 4.96%. Statistically significant differences were found only between Pleven and Stara Zagora (p = 0.002), but no significant differences in infection rates were observed between adults and nymphs in the regions examined. Overall, the prevalence of B. afzelii in each region exceeds that of B. garinii, and when considered collectively for Bulgaria, the frequency of B. afzelii (15.9%) is higher than that of B. garinii (10.89%) in infected ticks. In a controlled epidemiological context, managing the population of I. ricinus infected with B. burgdorferi s.l. can mitigate the health burden of Lyme disease, although this preventive strategy may not guarantee complete protection. Full article

(This article belongs to the Section Bacterial Pathogens)

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14 pages, 554 KB

Open AccessEditor’s ChoiceArticle

Systemic Inflammatory Indices (SII and SIRI) in 30-Day Mortality Risk Stratification for Community-Acquired Pneumonia: A Study Alongside CURB-65 and PSI

by Orkun Eray Terzi, Gülgün Çetintaş Afşar, Nazlı Çetin and Seyhan Dülger

Pathogens 2025, 14(12), 1235; https://doi.org/10.3390/pathogens14121235 - 3 Dec 2025

Cited by 3 | Viewed by 1355

Abstract

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide, underscoring the need for accessible and cost-effective biomarkers to support early risk assessment. This retrospective study investigated the prognostic performance of two systemic inflammatory indices—the Systemic Immune-Inflammation Index (SII) and the [...] Read more.

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide, underscoring the need for accessible and cost-effective biomarkers to support early risk assessment. This retrospective study investigated the prognostic performance of two systemic inflammatory indices—the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)—in 240 adults hospitalized with CAP between January and December 2024. The primary outcome was 30-day all-cause mortality. Logistic regression and receiver operating characteristic (ROC) analyses were applied to compare these indices with established severity scores, CURB-65 and the Pneumonia Severity Index (PSI). Thirty-day mortality occurred in 15.4% of patients. Non-survivors exhibited significantly higher SII values (p = 0.043) and a trend toward increased SIRI levels (p = 0.072). Both indices showed weak but statistically significant positive correlations with conventional inflammatory markers such as C-reactive protein and procalcitonin. While CURB-65 and PSI retained superior discriminative ability, SII and SIRI provided only modest prognostic information and did not significantly improve mortality prediction beyond these scores. These findings indicate that simple, hematology-based indices reflecting systemic inflammation may offer limited but potentially clinically relevant adjunctive information when integrated with traditional clinical scoring systems. Full article

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

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34 pages, 1885 KB

Open AccessEditor’s ChoiceReview

Oral Microbiota and Carcinogenesis: Exploring the Systemic Impact of Oral Pathogens

by Nađa Nikolić, Ana Pucar, Uroš Tomić, Sanja Petrović, Đorđe Mihailović, Aleksandar Jovanović and Milena Radunović

Pathogens 2025, 14(12), 1233; https://doi.org/10.3390/pathogens14121233 - 3 Dec 2025

Cited by 3 | Viewed by 2428

Abstract

For decades, cancer risk has been explained mainly by local factors. However, emerging evidence shows that the oral microbiome acts as a systemic modifier of oncogenesis well beyond the head and neck. This review synthesizes clinical and mechanistic data linking dysbiotic oral communities, [...] Read more.

For decades, cancer risk has been explained mainly by local factors. However, emerging evidence shows that the oral microbiome acts as a systemic modifier of oncogenesis well beyond the head and neck. This review synthesizes clinical and mechanistic data linking dysbiotic oral communities, especially Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, to malignancies across gastrointestinal, respiratory, hepatobiliary, pancreatic, breast, and urogenital systems. We summarize organ-specific associations from saliva, tissue, and stool studies, noting the recurrent enrichment of oral taxa in tumor and peri-tumoral niches of oral, esophageal, gastric, colorectal, lung, pancreatic, liver, bladder, cervical, and breast cancers. Convergent mechanisms include the following: (i) persistent inflammation (lypopolysacharide, gingipains, cytolysins, and collagenases); (ii) direct genotoxicity (acetaldehyde, nitrosation, and CDT); (iii) immune evasion/suppression (TLR/NLR signaling, MDSC recruitment, TAN/TAM polarization, and TIGIT/CEACAM1 checkpoints); and (iv) epigenetic/signaling rewiring (NF-κB, MAPK/ERK, PI3K/AKT, JAK/STAT, WNT/β-catenin, Notch, COX-2, and CpG hypermethylation). Plausible dissemination along an oral–gut–systemic axis, hematogenous, lymphatic, microaspiration, and direct mucosal transfer enables distal effects. While causality is not yet definitive, cumulative data support oral dysbiosis as a clinically relevant cofactor, motivating biomarker-based risk stratification, saliva/stool assays for early detection, and microbiome-targeted interventions (periodontal care, antimicrobials, probiotics, and microbiota modulation) alongside conventional cancer control. Full article

(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)

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28 pages, 4153 KB

Open AccessEditor’s ChoiceReview

Interspecies Transmission of Animal Rotaviruses to Humans: Reassortment-Driven Adaptation

by Toyoko Nakagomi and Osamu Nakagomi

Pathogens 2025, 14(12), 1230; https://doi.org/10.3390/pathogens14121230 - 2 Dec 2025

Cited by 2 | Viewed by 1266

Abstract

Rotavirus alphagastroenteritidis (rotavirus) infects a broad range of hosts, including humans and various animal species. Its genome comprises 11 segments of double-stranded RNA, making it highly prone to genetic diversity through gene reassortment. Although rotavirus strains are typically host-specific, novel human strains with [...] Read more.

Rotavirus alphagastroenteritidis (rotavirus) infects a broad range of hosts, including humans and various animal species. Its genome comprises 11 segments of double-stranded RNA, making it highly prone to genetic diversity through gene reassortment. Although rotavirus strains are typically host-specific, novel human strains with global impact often originate from interspecies transmission of animal rotaviruses. This review explores the critical role of interspecies transmission coupled with genetic reassortment in rotavirus adaptation to humans, contextualizing key studies and methodological advances. Central to this progress was the development of tools to analyse entire genomes and distinguish homologous from heterologous strains. We trace the evolution from RNA-RNA hybridisation to whole-genome sequencing, which underpins genotype constellation and sub-genotype phylogeny. A decade-long surveillance of the bovine-like G8 rotavirus in Vietnam offers a compelling model: for an animal rotavirus to become a successful human pathogen, it must replace its animal-derived genes with human-derived counterparts through reassortment. Retaining the animal-origin G8 VP7 gene is enabled by acquiring a compatible human VP4 gene (specifically P[8]) and DS-1-like backbone genes. Building on this model of reassortment-driven adaptation, our investigation into the unusual G1P[6] strain AU19, of wholly porcine origin, supports the hypothesis that the predominant human G1 rotavirus also evolved from a successful interspecies transmission event. Phylogenetic analysis suggests the ancestral human G1 gene emerged from a porcine rotavirus between 1915 and 1948, later reassorting with human strains to acquire Wa-like backbone genes, ultimately becoming a stable and dominant part of the human rotavirus population. In conclusion, genetic reassortment is a key mechanism transforming sporadic zoonotic events into sustained human-pathogens, although other factors remain to be fully defined. We conclude by highlighting key areas for further research. Full article

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24 pages, 2468 KB

Open AccessEditor’s ChoiceReview

The Paradox of Healthcare in the ‘Superbugs’ Era: Current Challenges and Future Directions

by Elenoire Sole, Marilena Trinchera, Silvia De Gaetano, Angelina Midiri, Giovanni Piccolo, Giuseppe Mancuso, Giovanni Schepici and Carmelo Biondo

Pathogens 2025, 14(12), 1199; https://doi.org/10.3390/pathogens14121199 - 24 Nov 2025

Cited by 2 | Viewed by 2137

Abstract

Antibiotic-resistant microbes represent a growing problem for modern medicine and public health. Projections indicate that deaths from such infections could reach 10 million per year by 2050. Healthcare associated infections (HAI) are among the most significant causes of mortality and morbidity in hospitals, [...] Read more.

Antibiotic-resistant microbes represent a growing problem for modern medicine and public health. Projections indicate that deaths from such infections could reach 10 million per year by 2050. Healthcare associated infections (HAI) are among the most significant causes of mortality and morbidity in hospitals, impacting millions of patients globally. The emergence of HAI is associated with resistance to antimicrobials, rapidly worsening the patient’s condition. Antimicrobial resistance determines unresponsiveness to treatment, which can ultimately lead to severe complications such as sepsis and shock. It is estimated that one in every ten patients are susceptible to infection during their stay in hospital, with the microorganism responsible for the infection frequently proving resistant to antibiotics. Among the latter, CRE (carbapenem-resistant Enterobacteriaceae), CRAB (carbapenem-resistant Acinetobacter baumannii), CRPA (carbapenem-resistant Pseudomonas aeruginosa), vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus (MRSA), commonly referred to as ‘superbugs’, are a major cause of HAIs. The aim of the present study is to provide a comprehensive overview of the global epidemiology of healthcare-associated infections, with particular emphasis on their incidence, distribution over time, and correlation with the socioeconomic status of different countries. Furthermore, the review aims to evaluate the effectiveness of current preventive strategies in reducing the incidence and mortality associated with HAIs. Full article

(This article belongs to the Special Issue Classic and Emerging Pathogens as a Cause of Healthcare-Associated Infections: Current Knowledge and Future Approaches)

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16 pages, 1120 KB

Open AccessEditor’s ChoiceArticle

Clinical Progression of Cardiac Chronic Trypanosoma cruzi Infection in a Long-Term Prospective Cohort from Rural Colombia

by Mario J. Olivera, Julián F. Porras-Villamil, Christian Toquica-Gahona and Màrius V. Fuentes

Pathogens 2025, 14(12), 1198; https://doi.org/10.3390/pathogens14121198 - 24 Nov 2025

Cited by 2 | Viewed by 1089

Abstract

Chronic Trypanosoma cruzi infection remains a major cause of preventable cardiomyopathy in Latin America, yet prospective data from endemic rural populations after the interruption of domestic transmission are limited. This study characterizes the long-term clinical evolution, treatment response, and cardiovascular outcomes of 80 [...] Read more.

Chronic Trypanosoma cruzi infection remains a major cause of preventable cardiomyopathy in Latin America, yet prospective data from endemic rural populations after the interruption of domestic transmission are limited. This study characterizes the long-term clinical evolution, treatment response, and cardiovascular outcomes of 80 adults with confirmed chronic infection from Mogotes, Santander, Colombia. Participants were followed from 2015 to 2023 by means of standardized clinical, electrocardiographic, echocardiographic, serological, and qPCR evaluations. The primary outcome was progression from the indeterminate to the cardiac form; secondary outcomes included worsening to advanced cardiomyopathy and cardiovascular events. During 422 person-years of follow-up (median 61.5 months), 14 participants (17.5%) experienced clinical progression (3.3 per 100 person-years) and seven (9%) died (1.7 per 100 person-years). Benznidazole treatment was initiated in 42 participants and completed by 34 (81%); only 4 of 34 (12%) remained qPCR-positive after one year, compared with 21% among untreated individuals. Progression from the indeterminate form occurred in one participant (0.7 per 100 person-years), whereas deterioration clustered among those with baseline cardiomyopathy. Despite low mortality, stage-dependent progression persisted, highlighting the need for early diagnosis, treatment adherence, and sustained molecular and cardiac monitoring in post-certification settings. These findings provide rare longitudinal evidence on chronic T. cruzi infection under real-world endemic conditions. Full article

(This article belongs to the Special Issue Parasitic Diseases in the Contemporary World)

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14 pages, 2425 KB

Open AccessEditor’s ChoiceArticle

High Seroprevalence of Feline Leishmaniosis (FeL) in Campania (Italy) Region: Current Epidemiological Scenario

by Valentina Foglia Manzillo, Ines Balestrino, Gaetano Oliva, Roberta Brunetti, Stefania Cavallo, Rosa D’Ambrosio, Roberta Pellicanò, Luisa Spadari, Lorella Barca, Federica Bruno, Maria Ortensia Montella, Maria Paola Maurelli, Nunzia Florindo, Manuela Gizzarelli, Mariele De Santi and Loredana Baldi

Pathogens 2025, 14(12), 1194; https://doi.org/10.3390/pathogens14121194 - 23 Nov 2025

Viewed by 723

Abstract

Feline leishmaniosis (FeL) is still considered an emerging and neglected disease. Cats, once considered accidental hosts, are now recognized as adjunctive reservoirs of the disease, especially in areas where canine (CanL) and human (HumL) leishmaniosis are widespread. Although often asymptomatic, infected cats could [...] Read more.

Feline leishmaniosis (FeL) is still considered an emerging and neglected disease. Cats, once considered accidental hosts, are now recognized as adjunctive reservoirs of the disease, especially in areas where canine (CanL) and human (HumL) leishmaniosis are widespread. Although often asymptomatic, infected cats could contribute to the transmission cycle of the parasite. Recent studies in Campania (Italy) have found a significant prevalence of feline infection, indicating the need to implement diagnostic and surveillance protocols to prevent the spread of the disease. The aim of the study was to outline the current scenario by studying the prevalence of FeL in Campania to identifying the potential zoonotic risk and in addition to validate the Immunofluorescence Antibody Test (IFAT) method for the diagnosis of leishmaniosis in cats. The study involved initially 702 cats; for each cat, a clinical record was compiled, including identification data, anamnesis, and clinical findings. Due to incomplete information, statistical analysis was performed only on a subset of 601 cats. A blood sample was collected to obtain serum/plasma specimens. When feasible, a lymph node fine-needle aspiration was performed. The observed seroprevalence rate was 32.1% (193/601), with a higher seroprevalence in outdoor cats and the presence of asymptomatic seropositive animals (28.0%;54/193), suggesting that felines may act as silent reservoirs of Leishmania infantum. An excellent result was obtained for the validation and standardization of the analytical IFAT method for the diagnosis of feline leishmaniasis; therefore, an inter-laboratory test has been carried out to establish the dilution cut-off at ≥1:80 as compatible with infection. Furthermore, a xenodiagnosis examination was conducted on a cat that was infected to more accurately evaluate the possibility of asymptomatic cats acting as carriers of the infection; however, this test resulted negative. Full article

(This article belongs to the Topic Zoonotic Vector-Borne Diseases of Companion Animals)

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10 pages, 384 KB

Open AccessEditor’s ChoiceArticle

Seroprevalence of Toxoplasma gondii, Neospora caninum and Encephalitozoon cuniculi in Red Foxes (Vulpes vulpes) from Italy

by Leonardo Brustenga, Stefano Scarcelli, Giulia Rigamonti, Iolanda Moretta, Manuela Diaferia, Giulia Morganti, Nicoletta D’Avino, Marco Gobbi, Alice Ranucci, Giovanni Sgroi, Fabrizio Passamonti and Fabrizia Veronesi

Pathogens 2025, 14(11), 1175; https://doi.org/10.3390/pathogens14111175 - 18 Nov 2025

Viewed by 1105

Abstract

The ecological role and overlap with urban environments make wild carnivores useful epidemiological sentinels for several pathogens. The present study aimed to investigate the seroprevalence of Toxoplasma gondii, Neospora caninum and Encephalitozoon cuniculi in red foxes (Vulpes vulpes) from Central [...] Read more.

The ecological role and overlap with urban environments make wild carnivores useful epidemiological sentinels for several pathogens. The present study aimed to investigate the seroprevalence of Toxoplasma gondii, Neospora caninum and Encephalitozoon cuniculi in red foxes (Vulpes vulpes) from Central and Southern Italy. Sera from 120 foxes were analyzed using IFAT with a 1:20 cut-off value. Overall, seropositivity was highest for T. gondii (68.5%), followed by E. cuniculi (15.0%) and N. caninum (3.3%). Multivariable logistic regression models with stepwise selection identified age class and location as significant predictor factors for T. gondii exposure, with adults and red foxes from Southern Italy showing higher levels of prevalence. No significant associations with epidemiological risk factors were detected for E. cuniculi or N. caninum. Co-infections were detected in 15% of red foxes with a statistically significant positive association between T. gondii and E. cuniculi. These findings highlight that red foxes, being scavengers, are particularly exposed to food-borne pathogens, especially to T. gondii, and prove once again that they are reliable epidemiological sentinels for parasites that circulate at the wild–domestic interface. Full article

(This article belongs to the Special Issue Pets, Wildlife and Parasites—2nd Edition)

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21 pages, 12771 KB

Open AccessEditor’s ChoiceArticle

Bovine Clinical E. coli Mastitis in Italian Dairy Herds Is Not Associated with a Specific Pathotype

by Giulia Laterza, Gabriele Meroni, Alessio Soggiu, Piera Anna Martino, Valerio Massimo Sora, Francesca Zaghen, Luigi Bonizzi, Luciana Colombo and Alfonso Zecconi

Pathogens 2025, 14(11), 1181; https://doi.org/10.3390/pathogens14111181 - 18 Nov 2025

Viewed by 921

Abstract

Background: Escherichia coli is a cause of severe clinical bovine mastitis; however, it is not yet fully understood what makes mastitis-associated bacteria different from commensal strains at the genetic level. The goal of this study was to compare the genomic features, sequence types, [...] Read more.

Background: Escherichia coli is a cause of severe clinical bovine mastitis; however, it is not yet fully understood what makes mastitis-associated bacteria different from commensal strains at the genetic level. The goal of this study was to compare the genomic features, sequence types, virulence, and antibiotic resistance profiles of E. coli isolated from healthy cows and cows with clinical mastitis in Northern Italy. Methods: Between 2023 and 2024, 46 E. coli isolates, 23 from healthy animals and 23 from mastitis cases were recovered. Standard phenotypic approaches and Oxford Nanopore sequencing were used to investigate the genomic landscape of the strains. Results: Phylogroups A and B1 were the most common in both groups. MLST showed several types, with ST10 (19.6%), ST58 (13.0%), and ST69 (8.7%) being the most common. There was no lineage that was uniquely able to describe the isolates as Mammary Pathogenic Escherichia coli (MPEC); indeed, the ST distribution and phylogeny were the same in both groups. A total of 47.8% of isolates had antimicrobial resistance determinants, with β-lactamases (21.7%) and tetA (15.2%) being the most common. No significant differences in resistance rates were observed between mastitis and healthy isolates. Pangenome investigation found a large pool of accessory genes, but no genomic signature that distinguished mastitis from commensal isolates across the MPEC. Conclusions: Bovine E. coli isolated from milk of both healthy and mastitic cows share sequence types, resistance rates, and accessory genome content, supporting the absence of a unique MPEC pathotype and highlighting the ecological versatility of these bacteria. Full article

(This article belongs to the Section Bacterial Pathogens)

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16 pages, 2671 KB

Open AccessEditor’s ChoiceArticle

Bactericidal Activity of Pradofloxacin and Other Antimicrobials Against Swine Respiratory Bacterial Pathogens

by Joseph M. Blondeau and Shantelle D. Fitch

Pathogens 2025, 14(11), 1171; https://doi.org/10.3390/pathogens14111171 - 17 Nov 2025

Viewed by 754

Abstract

Swine respiratory disease (SRD) is a complex interaction whereby viral infection predisposes the host to secondary bacterial pulmonary invasion, which may be fatal. Antimicrobial agents remain an important therapy and serve to reduce morbidity and mortality in treated animals. Pradofloxacin is the newest [...] Read more.

Swine respiratory disease (SRD) is a complex interaction whereby viral infection predisposes the host to secondary bacterial pulmonary invasion, which may be fatal. Antimicrobial agents remain an important therapy and serve to reduce morbidity and mortality in treated animals. Pradofloxacin is the newest of the veterinary antibiotics to be approved to treat SRD. It is a dual-targeting fluoroquinolone with in vitro and clinical activity against Gram-negative and -positive bacteria, along with atypical agents including anaerobes. In this study, we compared the killing of Actinobacillus pleuropneumoniae, Pasteurella multocida, and Streptococcus suis by pradofloxacin and comparator antibiotics in a 3 h kill assay, using four clinically relevant drug concentrations. Pradofloxacin was bactericidal against the three pathogens, with kill rates ranging from 94.4 to 99.9% (A. pleuropneumoniae) following 15–20 min of exposure to the maximum serum and maximum tissue drug concentration. For P. multocida, the kill rates were 68.7–96.9% following 5–30 min of drug exposure at the maximum serum drug concentration, and 91.7% following 5 min of drug exposure at the maximum tissue drug concentration. For S. suis, pradofloxacin killed 92.4–99.4% and 71.6–97.1% of cells following 60–180 min of drug exposure at the maximum serum and maximum tissue drug concentration, respectively. Pradofloxacin appears to be an important addition to the drugs currently available for treating SRD. Full article

(This article belongs to the Special Issue Diagnostics, Antimicrobial Resistance, and Emerging Bacterial Pathogens)

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17 pages, 1266 KB

Open AccessEditor’s ChoiceArticle

Malassezia pachydermatis Acquires Resistance to Polyenes in the Laboratory Model

by Urszula Czyżewska, Sandra Chmielewska, Marek Bartoszewicz and Adam Tylicki

Pathogens 2025, 14(11), 1162; https://doi.org/10.3390/pathogens14111162 - 14 Nov 2025

Cited by 1 | Viewed by 1561

Abstract

This study presents a model investigation into the development of tolerance to polyene antifungal drugs (nystatin and natamycin) in strains of Malassezia pachydermatis. This species, commonly associated with external ear canal infections in dogs, has emerged as increasingly significant in the broader [...] Read more.

This study presents a model investigation into the development of tolerance to polyene antifungal drugs (nystatin and natamycin) in strains of Malassezia pachydermatis. This species, commonly associated with external ear canal infections in dogs, has emerged as increasingly significant in the broader context of growing fungal resistance to treatment. In the experiment, 10 strains of M. pachydermatis were passaged over a period of 105 weeks on media containing sublethal concentrations of nystatin and natamycin. Minimal inhibitory (MIC) and minimal fungicidal concentration (MFC) values were regularly assessed to monitor tolerance development. The results revealed a varied response among the strains: Some were eliminated during the process, while others showed a gradual increase in MIC values, up to fivefold in the case of nystatin. In several strains, acquired resistance remained stable even after passaging in drug-free conditions, whereas others reverted to their original susceptibility. The model demonstrated that resistance does not emerge immediately; significant changes appeared only after 30–45 passages. The authors propose this model as a valuable tool for tracking sequential changes that lead to resistance development. Such an approach may support targeted therapy development and help identify strains predisposed to drug adaptation. These findings hold promise for assessing therapeutic risk in immunosuppressed patients and for building resistance datasets that can support artificial intelligence algorithms in predicting fungal resistance mechanisms. Full article

(This article belongs to the Section Fungal Pathogens)

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14 pages, 1909 KB

Open AccessEditor’s ChoiceArticle

Role of S1PR1 in Modulating Airway Epithelial Responses to Pseudomonas aeruginosa in Cystic Fibrosis

by Cristina Cigana, Claudia Caslini, Alessandro Migliara, Beatriz Alcala’-Franco, Laura Veschetti, Nicola Ivan Lorè, Angelo Lombardo and Alessandra Bragonzi

Pathogens 2025, 14(11), 1146; https://doi.org/10.3390/pathogens14111146 - 12 Nov 2025

Viewed by 825

Abstract

Background: Pseudomonas aeruginosa infection is a major driver of morbidity and mortality in cystic fibrosis (CF), yet disease severity varies widely among people with CF (pwCF). This clinical heterogeneity suggests the involvement of host genetic modifiers beyond CFTR. We previously identified [...] Read more.

Background: Pseudomonas aeruginosa infection is a major driver of morbidity and mortality in cystic fibrosis (CF), yet disease severity varies widely among people with CF (pwCF). This clinical heterogeneity suggests the involvement of host genetic modifiers beyond CFTR. We previously identified sphingosine 1-phosphate receptor 1 (S1PR1) as a candidate gene associated with susceptibility to P. aeruginosa. Here, we investigated its role in modulating airway epithelial responses to infection. Methods: Using CRISPR/Cas9, we generated S1PR1-knockout bronchial epithelial cells with (IB3-1) and without (C38) CFTR mutations. We assessed cell viability, cytotoxicity, and interleukin-8 secretion following exposure to P. aeruginosa exoproducts. S1PR1 protein expression was evaluated in lung tissue from pwCF and non-CF individuals using immunohistochemistry. Results: S1PR1-mutant cells produced truncated, non-functional peptides. In CFTR-mutant cells, S1PR1 loss reduced viability, increased cytotoxicity, and significantly enhanced interleukin-8 production in response to P. aeruginosa exoproducts. These effects were not observed in CFTR-competent cells. Notably, S1PR1 protein levels were markedly lower in lung tissue from pwCF compared to non-CF individuals. Conclusions: S1PR1 deficiency exacerbates epithelial damage and inflammatory responses to P. aeruginosa in CF models. These findings highlight S1PR1 as a potential contributor to infection severity and a promising target for therapeutic strategies in pwCF. Full article

(This article belongs to the Special Issue The Host-Pathogen Interaction in Cystic Fibrosis)

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27 pages, 19107 KB

Open AccessEditor’s ChoiceReview

Zika Virus: A Tale of Two Lineages

by Inès Bribes and Sébastien Nisole

Pathogens 2025, 14(11), 1151; https://doi.org/10.3390/pathogens14111151 - 12 Nov 2025

Viewed by 2218

Abstract

Zika virus (ZIKV) was first identified in Africa in the mid-20th century and circulated for decades with limited and often unnoticed human cases. This situation changed with the emergence of the Asian lineage, responsible for large outbreaks in the Pacific and the Americas [...] Read more.

Zika virus (ZIKV) was first identified in Africa in the mid-20th century and circulated for decades with limited and often unnoticed human cases. This situation changed with the emergence of the Asian lineage, responsible for large outbreaks in the Pacific and the Americas and for severe complications such as Guillain–Barré syndrome and Congenital Zika Syndrome (CZS). In contrast, the African lineage, although frequently more efficient in replication, cytopathogenicity, and mosquito transmission in experimental systems, has not been linked to comparable epidemics or congenital disease clusters. This review summarizes current knowledge on the differences between African and Asian lineages at the molecular, cellular, and epidemiological levels. It highlights how genetic variation interacts with host immunity, ecological factors, and human activity to shape epidemic potential. Understanding these interactions is essential for anticipating future outbreaks and for improving strategies to mitigate the impact of emerging arboviruses. Full article

(This article belongs to the Special Issue Epidemiology of Vector-Borne Pathogens)

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23 pages, 985 KB

Open AccessEditor’s ChoiceReview

Nature-Inspired Pathogen and Cancer Protein Covalent Inhibitors: From Plants and Other Natural Sources to Drug Development

by Giovanni N. Roviello

Pathogens 2025, 14(11), 1153; https://doi.org/10.3390/pathogens14111153 - 12 Nov 2025

Cited by 7 | Viewed by 2076

Abstract

Nature has long served as a prolific source of bioactive compounds, offering structurally diverse scaffolds for the development of therapeutics. In recent years, increasing attention has been given to nature-inspired covalent inhibitors, molecules that form covalent bonds with pathogen- or cancer-specific targets, due [...] Read more.

Nature has long served as a prolific source of bioactive compounds, offering structurally diverse scaffolds for the development of therapeutics. In recent years, increasing attention has been given to nature-inspired covalent inhibitors, molecules that form covalent bonds with pathogen- or cancer-specific targets, due to their potential selectivity and sustained biological activity. This review explores the landscape of covalent inhibitors derived from natural sources, with a focus on compounds from fungi, marine organisms, bacteria and plants. In particular, emphasis is placed on the molecular mechanisms through which these compounds exert their activity against different types of pathogens and other biomedically relevant targets, highlighting key structural motifs that facilitate covalent interactions. Furthermore, the review discusses recent advances in synthetic modification, target identification, and optimization strategies that bridge natural compound discovery with modern drug development. By drawing insights from nature’s chemical repertoire, this work ultimately displays the potential of natural covalent inhibitors as a promising foundation for next-generation anti-infective and anticancer therapeutics. Full article

(This article belongs to the Special Issue Covalent Inhibitors of Pathogenic Bacterial, Protozoal, Viral, and Fungal Targets)

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13 pages, 1484 KB

Open AccessEditor’s ChoiceArticle

Stage-Specific Expression and Subcellular Localization of Calcineurin in Infective Forms of Leishmania amazonensis

by Deborah Brandt-Almeida, Ismael Pretto Sauter, Mario Costa Cruz, Cristian Cortez, Patricio Reyes Orrego and Mauro Cortez

Pathogens 2025, 14(11), 1139; https://doi.org/10.3390/pathogens14111139 - 10 Nov 2025

Viewed by 863

Abstract

Calcineurin (CaN), a Ca²⁺-dependent phosphatase, plays key roles in eukaryotic cell signaling. We investigated whether Leishmania amazonensis’ two infective forms—promastigotes and amastigotes—exhibit differences in CaN expression, localization, and functional impact, using two canonical inhibitors (cyclosporin A, CsA; tracolimus, FK506). At [...] Read more.

Calcineurin (CaN), a Ca²⁺-dependent phosphatase, plays key roles in eukaryotic cell signaling. We investigated whether Leishmania amazonensis’ two infective forms—promastigotes and amastigotes—exhibit differences in CaN expression, localization, and functional impact, using two canonical inhibitors (cyclosporin A, CsA; tracolimus, FK506). At high 40 µM CsA, promastigotes showed reduced viability, whereas amastigotes remained resistant. FK506 had no effect on either form. At a sub-lethal 25 µM CsA, parasite proliferation remained unaffected. In parasite–macrophage co-incubation assays, phosphorylation patterns differed: amastigotes—but not promastigotes—showed increased serine/threonine phosphorylation upon CaN inhibition. Western blotting and in silico data revealed higher CaN catalytic (CaNA2) and regulatory (CaNB) subunit expression in amastigotes than promastigotes. Immunofluorescence localized CaNA prominently in both cytoplasm and nucleus of promastigotes, but predominantly cytoplasmic in amastigotes; CaNB was largely cytoplasmic in both. In silico localization predictions suggested strong membrane associations for CaNA in Leishmania, contrasting with mammalian models. Subcellular fractionation confirmed CaNA enrichment in membrane fractions, with CaNB in cytoplasmic and nuclear fractions. Collectively, these findings reveal form-specific differences in expression, subcellular distribution, and inhibitor responses of CaN in L. amazonensis, highlighting its potential as a stage-specific therapeutic target in leishmaniasis. Full article

(This article belongs to the Special Issue Virulence and Molecular Cell Biology of Parasites)

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18 pages, 2769 KB

Open AccessEditor’s ChoiceReview

Advancing Laboratory Diagnostics for Future Pandemics: Challenges and Innovations

by Lechuang Chen and Qing H. Meng

Pathogens 2025, 14(11), 1135; https://doi.org/10.3390/pathogens14111135 - 9 Nov 2025

Cited by 4 | Viewed by 2982

Abstract

Since the beginning of the 21st century, major epidemics and pandemics such as SARS, H1N1pdm09, Ebola, and COVID-19 have repeatedly challenged global systems of disease diagnostics and control. These crises exposed the weaknesses of traditional diagnostic models, including long turnaround times, uneven resource [...] Read more.

Since the beginning of the 21st century, major epidemics and pandemics such as SARS, H1N1pdm09, Ebola, and COVID-19 have repeatedly challenged global systems of disease diagnostics and control. These crises exposed the weaknesses of traditional diagnostic models, including long turnaround times, uneven resource distribution, and supply chain bottlenecks. As a result, there is an urgent need for more advanced diagnostic technologies and integrated diagnostics strategies. Our review summarizes key lessons learned from four recent major outbreaks and highlights advances in diagnostic technologies. Among these, molecular techniques such as loop-mediated isothermal amplification (LAMP), transcription-mediated amplification (TMA), recombinase polymerase amplification (RPA), and droplet digital polymerase chain reaction (ddPCR) have demonstrated significant advantages and are increasingly becoming core components of the detection framework. Antigen testing plays a critical role in rapid screening, particularly in settings such as schools, workplaces, and communities. Serological assays provide unique value for retrospective outbreak analysis and assessing population immunity. Next-generation sequencing (NGS) has become a powerful tool for identifying novel pathogens and monitoring viral mutations. Furthermore, point-of-care testing (POCT), enhanced by miniaturization, biosensing, and artificial intelligence (AI), has extended diagnostic capacity to the front lines of epidemic control. In summary, the future of epidemic and pandemic response will not depend on a single technology, but rather on a multi-layered and complementary system. By combining laboratory diagnostics, distributed screening, and real-time monitoring, this system will form a global diagnostic network capable of rapid response, ensuring preparedness for the next global health crisis. Full article

(This article belongs to the Special Issue Leveraging Technological Advancement for Pandemic Preparedness)

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20 pages, 8138 KB

Open AccessEditor’s ChoiceArticle

Reverse Genetic Analyses of Hydrophobins in Sclerotinia sclerotiorum Revealed Their Diverse Roles in Development, Environmental Survival, and Virulence

by Jinyi Tan, Zhengxi Gong, Xinyi Huang, Shawn D. Mansfield and Xin Li

Pathogens 2025, 14(11), 1131; https://doi.org/10.3390/pathogens14111131 - 6 Nov 2025

Viewed by 931

Abstract

Sclerotinia sclerotiorum is a notorious soilborne fungal pathogen that causes white mold in a wide range of host plants, leading to globally significant yield loss in many crops. Hydrophobins (HPs) are small, secreted proteins unique to filamentous fungi, with diverse roles in fungal [...] Read more.

Sclerotinia sclerotiorum is a notorious soilborne fungal pathogen that causes white mold in a wide range of host plants, leading to globally significant yield loss in many crops. Hydrophobins (HPs) are small, secreted proteins unique to filamentous fungi, with diverse roles in fungal biology. However, their functions in S. sclerotiorum remain poorly understood. Here, we systematically investigated the roles of three HP genes, SsHP1, SsHP2, and SsHP3, through reverse genetic analyses. By analyzing their deletion mutant phenotypes, we demonstrate that class I HP (SsHP1) is specifically required for proper sclerotia development, whereas class II HPs (SsHP2 and SsHP3) are essential for compound appressoria functionality. All three HPs contribute to fungal surface hydrophobicity, cell wall integrity, and stress tolerance. Using mycelial fusion, we generated double mutants lacking both class II HPs, which exhibited more severe defects in appressoria development, virulence, cell wall integrity, and stress adaptation, indicating their partially redundant roles. SsHP2 is required for both host penetration and post-penetration virulence, whereas SsHP3 mainly affects host penetration, revealing their overlapping yet distinct contributions to pathogenic development. Although all HP mutants formed normal apothecia and asci, they released significantly fewer ascospores, suggesting that HPs are dispensable for sexual morphogenesis but crucial for the biophysical process of ascospore dispersal. Furthermore, carbohydrate analyses uncovered that these HPs affect cell wall composition, more broadly influencing stress adaptation and virulence. Taken together, our study reveals both conserved and divergent roles of HPs across fungi and highlight their multifaceted contributions to S. sclerotiorum biology, offering new perspectives for disease management. Full article

(This article belongs to the Special Issue Filamentous Fungal Pathogens: 2nd Edition)

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11 pages, 1329 KB

Open AccessEditor’s ChoiceArticle

Genetic Diversity of Stenotrophomonas maltophilia and Clonal Transmission (ST92) in Critical Care Units at Hospital Juárez de México: MLST and Virulence Profiling

by Liliana Nicolas-Sayago, Clemente Cruz-Cruz, Emilio M. Durán-Manuel, Graciela Castro-Escarpulli, María G. Ortíz-López, Carlos A. Jiménez-Zamarripa, Araceli Rojas-Bernabé, Nayeli G. Nieto-Velázquez, Eduardo Tolentino-Sánchez, Juan C. Bravata-Alcántara, Julio C. Castañeda-Ortega, Benito Hernández-Castellanos, Adolfo López-Ornelas, Laura M. Márquez-Valdelamar, Dulce M. Razo Blanco-Hernández, Jonathan Puente-Rivera, Claudia C. Calzada-Mendoza, Yahaira de J. Tamayo-Ordóñez, María C. Tamayo-Ordóñez, Francisco A. Tamayo-Ordóñez, Miguel Á. Loyola-Cruz and Juan M. Bello-López Show full author list Hide full author list

Pathogens 2025, 14(11), 1125; https://doi.org/10.3390/pathogens14111125 - 5 Nov 2025

Cited by 3 | Viewed by 1584

Abstract

Stenotrophomonas maltophilia is considered one of the emerging bacterial agents causing healthcare-associated infections (HAIs) in hospital environments. This microorganism has been identified as multidrug-resistant, capable of forming mature biofilms—an ability that promotes adherence to surfaces and invasive medical devices, favoring persistence in hospital [...] Read more.

Stenotrophomonas maltophilia is considered one of the emerging bacterial agents causing healthcare-associated infections (HAIs) in hospital environments. This microorganism has been identified as multidrug-resistant, capable of forming mature biofilms—an ability that promotes adherence to surfaces and invasive medical devices, favoring persistence in hospital environments and the potential to generate outbreaks. The aim of this study was to characterize S. maltophilia strains isolated from HAI cases at the Hospital Juárez de México and to determine the presence of hidden outbreaks. Antibiotic resistance profiles were determined, along with the typing of 20 genes associated with virulence factors and the assessment of the ability to form mature biofilms on inert surfaces. Finally, sequence type (ST) was obtained through multilocus sequence typing (MLST) analysis, and a phylogenetic tree was constructed to determine the clonal diversity of the isolates. All strains showed uniform resistance to β-lactam antibiotics tested while remaining sensitive to fluoroquinolones, phenicols, tetracyclines, and trimethoprim/sulfamethoxazole. Some isolates exhibited adherent activity, with the “strong biofilm-former” phenotype predominating. Sixteen virulence-related genes were heterogeneously detected, revealing broad genetic diversity. MLST analysis grouped the isolates into nine ST related to infection cases reported in others countries. Phylogenetic analyses demonstrated the presence of three potential clones distributed across Internal Medicine and the Pediatric Intensive Care Unit. These results highlight the importance of investigating S. maltophilia as an HAI-associated pathogen that remains understudied. Full article

(This article belongs to the Section Bacterial Pathogens)

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28 pages, 2097 KB

Open AccessEditor’s ChoiceReview

The Human Archaeome: Commensals, Opportunists, or Emerging Pathogens?

by Douglas M. Ruden

Pathogens 2025, 14(11), 1111; https://doi.org/10.3390/pathogens14111111 - 31 Oct 2025

Cited by 2 | Viewed by 1908

Abstract

Archaea, one of the three domains of life, are increasingly recognized as consistent, though often underappreciated, members of the human microbiome, yet their roles in health and disease remain poorly understood. Unlike bacteria, no archaeal species have been conclusively identified as primary mammalian [...] Read more.

Archaea, one of the three domains of life, are increasingly recognized as consistent, though often underappreciated, members of the human microbiome, yet their roles in health and disease remain poorly understood. Unlike bacteria, no archaeal species have been conclusively identified as primary mammalian pathogens, but their widespread presence across diverse body sites suggests potential indirect contributions to host physiology and pathology. Current evidence is synthesized on archaeal diversity and habitat specificity across multiple human-associated sites, encompassing the gastrointestinal, aerodigestive, and urogenital tracts as well as the skin. Methanogens dominate the lower gastrointestinal tract (LGT), where they influence fermentation dynamics and methane production, while members of the class Nitrososphaeria are prevalent on the skin and upper aerodigestive tract (UAT), reflecting ecological specialization. Variability in archaeal composition across niches highlights possible links to disease processes: methanogens have been associated with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, and colorectal cancer (CRC); Methanobrevibacter oralis is enriched in periodontal disease; and archaea have been detected in the lungs of cystic fibrosis patients. Although archaea lack canonical bacterial virulence factors, they may contribute indirectly through metabolic cross-feeding, immune modulation, synergy in polymicrobial infections, and alteration of host–microbiome network dynamics. This review explores the emerging concept of the human “archaeome”, evaluates current evidence for archaeal involvement in disease, and highlights emerging technologies, such as bacteria-MERFISH and multi-omics profiling, that enable translational applications including microbiome diagnostics, therapeutic targeting, and microbiome engineering. Full article

(This article belongs to the Special Issue Diagnosis, Immunopathogenesis and Control of Bacterial Infections)

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15 pages, 608 KB

Open AccessEditor’s ChoiceReview

A Comprehensive Review of Nanoparticles in the Fight Against Antimicrobial Resistance

by Antonios Mouzakis, Periklis Panagopoulos, Dimitrios Papazoglou and Vasileios Petrakis

Pathogens 2025, 14(11), 1090; https://doi.org/10.3390/pathogens14111090 - 26 Oct 2025

Cited by 12 | Viewed by 4440

Abstract

(1) Background: The escalating crisis of multidrug-resistant (MDR) bacteria presents a formidable threat to global public health, necessitating the urgent development of alternative antimicrobial strategies. Nanoparticles (NPs) have emerged as a promising frontier in this effort, leveraging their unique physicochemical properties and multi-modal [...] Read more.

(1) Background: The escalating crisis of multidrug-resistant (MDR) bacteria presents a formidable threat to global public health, necessitating the urgent development of alternative antimicrobial strategies. Nanoparticles (NPs) have emerged as a promising frontier in this effort, leveraging their unique physicochemical properties and multi-modal mechanisms of action to combat bacterial infections. This systematic review aims to comprehensively evaluate the current body of evidence on the dynamic interplay between nanoparticles and bacterial resistance. (2) Methods: A comprehensive search of electronic databases, including PubMed, Scopus, and Web of Science, was performed using a combination of keywords and Medical Subject Headings (MeSH) terms to identify relevant primary research articles. Eligibility criteria focused on studies evaluating the antimicrobial effects of nanoparticles on MDR bacterial strains, reporting on mechanisms of action, efficacy, or resistance development. (3) Results: The synthesis of findings revealed that nanoparticles exert their antimicrobial effects through multiple pathways, including the generation of reactive oxygen species (ROS), direct disruption of bacterial membranes, and the release of toxic ions. However, the analysis also confirmed that bacteria have evolved sophisticated defense mechanisms against nanoparticles, including surface modifications that prevent adhesion, upregulation of efflux pumps, and chemical neutralization of toxic ions. (4) Conclusions: Nanoparticles represent a potent and versatile tool in the global effort to combat antimicrobial resistance. Their long-term efficacy is not guaranteed, as bacteria have shown a remarkable capacity for adaptation. The future of this field lies in the development of rationally designed nanoparticle systems that not only possess intrinsic antimicrobial activity but also actively disarm bacterial resistance mechanisms. This includes the strategic use of synergistic combinations with conventional antibiotics and the exploration of resistance-agnostic approaches like nanotoxoid vaccines. Full article

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15 pages, 2396 KB

Open AccessEditor’s ChoiceArticle

Description of Sarcocystis arvalis n. sp. from the Common Vole (Microtus arvalis) in Lithuania Using Morphological and Molecular Methods

by Dovilė Laisvūnė Bagdonaitė, Eglė Rudaitytė-Lukošienė, Vitalijus Stirkė, Linas Balčiauskas, Dalius Butkauskas and Petras Prakas

Pathogens 2025, 14(11), 1086; https://doi.org/10.3390/pathogens14111086 - 24 Oct 2025

Cited by 2 | Viewed by 1166

Abstract

Records of Sarcocystis spp. diversity in rodents are relatively extensive; however, the increasing application of molecular approaches indicates that our current knowledge of these parasites remains incomplete. In the present study, morphological, genetic and phylogenetic data are provided on Sarcocystis arvalis n. sp. [...] Read more.

Records of Sarcocystis spp. diversity in rodents are relatively extensive; however, the increasing application of molecular approaches indicates that our current knowledge of these parasites remains incomplete. In the present study, morphological, genetic and phylogenetic data are provided on Sarcocystis arvalis n. sp. from the common vole (Microtus arvalis). Using light microscopy, the observed sarcocysts had a relatively thin (<1 μm) and smooth cyst wall. Via transmission electron microscopy, the sarcocyst wall thickness ranged from 0.7 to 1 μm, and the parasitophorous vacuolar membrane exhibited small knob-like blebs and was slightly wavy, type 1a. Based on 18S rRNA, 28S rRNA, cox1 and rpoB loci, S. arvalis n. sp. showed the highest similarity with Sarcocystis myodes from the bank vole (Clethronomys glareolus). According to the phylogenetic placement, S. arvalis n. sp. is the most closely related to Sarcocystis spp. with a rodent–mammal lifecycle. Morphologically, S. arvalis n. sp. forms sarcocysts that share a lot of similarities with those of S. myodes, Sarcocystis ratti and Sarcocystis cernae and molecular analysis is necessary for accurate species identification. Based on the abundance of the hosts and the proportion of voles in their diet, the most likely definitive hosts of S. arvalis n. sp. are red foxes, stone martens, least weasels, and domestic cats. Full article

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14 pages, 4253 KB

Open AccessEditor’s ChoiceArticle

Immunopathological Changes Caused by Oesophagostomum radiatum in Calves: Insights into Host–Parasite Interactions

by Cesar Cristiano Bassetto, Ana Cláudia Alexandre de Albuquerque, José Gabriel Gonçalves Lins, Guilherme Fernandes Dias Canalli, Anandra Kauára dos Santos Gomes and Alessandro Francisco Talamini Amarante

Pathogens 2025, 14(11), 1074; https://doi.org/10.3390/pathogens14111074 - 22 Oct 2025

Viewed by 1354

Abstract

The intensity and prevalence of different gastrointestinal nematode species vary across regions worldwide. Oesophagostomum radiatum commonly shows a high occurrence in young cattle. O. radiatum causes anaemia, hypoproteinaemia, and immunopathological changes in the large intestine wall, impairing calves’ body weight gain. This study [...] Read more.

The intensity and prevalence of different gastrointestinal nematode species vary across regions worldwide. Oesophagostomum radiatum commonly shows a high occurrence in young cattle. O. radiatum causes anaemia, hypoproteinaemia, and immunopathological changes in the large intestine wall, impairing calves’ body weight gain. This study aimed to assess the impact of natural O. radiatum infection on haematological parameters and immune responses in 23 Nellore calves, considering sex-based differences. Assessments included Oesophagostomum egg count (EPG), worm count, packed cell volume (PCV), total plasma protein, histopathological and immunohistochemistry analyses. A large number of parasites attached to the colon mucosa were observed, along with massive nodule formation and haemorrhagic lesions, mainly within a 20–30 cm-long segment adjacent to the nodules. The maximum mean egg shedding was approximately 165 EPG for males and 173 EPG for female calves; however, males presented a significantly higher worm count (969 ± 200.5) than females (460 ± 99.5). There were significant positive correlations between the total O. radiatum worm count and O. radiatum EPG for both female and male calves. Significant negative correlations were observed between the total O. radiatum worm count and PCV in female calves. Our results demonstrated that natural O. radiatum infection in Nellore calves induced marked immunopathological alterations, including chronic inflammatory responses that impaired intestinal function. Sex-related differences suggested that female calves may develop more effective tissue responses. These findings emphasise the economic impact of subclinical infections and reinforce the importance of control strategies to minimise productivity losses in cattle. Full article

(This article belongs to the Special Issue Parasitic Diseases in Livestock: Advances in Diagnostics, Understanding and Control)

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17 pages, 2606 KB

Open AccessEditor’s ChoiceReview

Plasmid Genomic Dynamics and One Health: Drivers of Antibiotic Resistance and Pathogenicity

by Célia P. F. Domingues, João S. Rebelo, Francisco Dionisio and Teresa Nogueira

Pathogens 2025, 14(10), 1054; https://doi.org/10.3390/pathogens14101054 - 18 Oct 2025

Cited by 1 | Viewed by 3107

Abstract

Seen through a One Health perspective, plasmids act as global links, connecting human, animal, and environmental microbiomes while broadening the ecological scope of resistance and virulence. By combining knowledge about plasmid classification, mobility, resistance, virulence, and data sources, this review emphasizes their key [...] Read more.

Seen through a One Health perspective, plasmids act as global links, connecting human, animal, and environmental microbiomes while broadening the ecological scope of resistance and virulence. By combining knowledge about plasmid classification, mobility, resistance, virulence, and data sources, this review emphasizes their key role as drivers of bacterial evolution and worldwide health risks. Recognizing plasmids as connectors across microbiomes highlights both the urgency and opportunity to address plasmid-mediated resistance with integrated strategies. Current plasmid databases, such as NCBI RefSeq, PLSDB, IMG/PR, and PlasmidScope, have already greatly advanced our understanding of these connections, and they are likely to profoundly alter how we see plasmid biology and One Health relationships. Full article

(This article belongs to the Special Issue Bacterial Pathogenesis and Antibiotic Resistance)

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25 pages, 1246 KB

Open AccessEditor’s ChoiceReview

Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities

by María Victoria Delpino and Jorge Quarleri

Pathogens 2025, 14(10), 1045; https://doi.org/10.3390/pathogens14101045 - 16 Oct 2025

Cited by 2 | Viewed by 8044

Abstract

We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and [...] Read more.

We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms—including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming—contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation. Full article

(This article belongs to the Special Issue Pathogen–Host Interactions: Death, Defense, and Disease)

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55 pages, 3869 KB

Open AccessEditor’s ChoiceReview

A Review of the Biology of Chikungunya Virus Highlighting the Development of Current Novel Therapeutic and Prevention Approaches

by Geovana Martelossi-Cebinelli, Jessica A. Carneiro, Kelly M. Yaekashi, Mariana M. Bertozzi, Beatriz H. S. Bianchini, Fernanda S. Rasquel-Oliveira, Camila Zanluca, Claudia N. Duarte dos Santos, Rachel Arredondo, Tiffani A. Blackburn, Rubia Casagrande and Waldiceu A. Verri

Pathogens 2025, 14(10), 1047; https://doi.org/10.3390/pathogens14101047 - 16 Oct 2025

Cited by 4 | Viewed by 6549

Abstract

Chikungunya virus (CHIKV) is an arthritogenic alphavirus transmitted primarily via Aedes aegypti and Aedes albopictus mosquitoes. Since its identification, CHIKV remained confined to parts of Africa and Asia until the early 2000s, when it expanded to other continents, causing epidemics. Structurally, it is [...] Read more.

Chikungunya virus (CHIKV) is an arthritogenic alphavirus transmitted primarily via Aedes aegypti and Aedes albopictus mosquitoes. Since its identification, CHIKV remained confined to parts of Africa and Asia until the early 2000s, when it expanded to other continents, causing epidemics. Structurally, it is an enveloped virus with a positive-single-stranded RNA genome, which encodes four non-structural proteins (nsP1-nsP4), responsible for viral replication, and five structural proteins (C, E3, E2, 6K, and E1), which form the capsid and envelope. Of these proteins, glycoproteins E1 and E2 are essential for cell recognition and membrane fusion, determining infectivity and viral tropism. CHIKV replication occurs in the cytosol of different cell types, triggering an intense inflammatory and immune response, which manifests clinically as Chikungunya fever (CHIKF). Despite its epidemiological impact, current treatment is limited to symptomatic approaches, including the use of analgesics and anti-inflammatories, as no specific antiviral therapies are available. In response, promising advances are being made, including the development of vaccines, targeted antivirals, and immunotherapies. This article aims to review the main aspects of viral biology, epidemiology, and immunopathogenesis of CHIKV infection, in addition to discussing the main advances in the development of new therapeutic approaches for its control. Full article

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

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20 pages, 3708 KB

Open AccessEditor’s ChoiceArticle

Bacillus anthracis Phylogeography: Origin of the East Asian Polytomy and Impact of International Trade for Its near Global Dispersal

by Gilles Vergnaud, Markus H. Antwerpen and Gregor Grass

Pathogens 2025, 14(10), 1041; https://doi.org/10.3390/pathogens14101041 - 14 Oct 2025

Viewed by 1276

Abstract

Bacillus anthracis is the etiological agent of the zoonotic disease anthrax. The pathogen has colonized many regions of all inhabited continents. Increasing evidence points to a strong contribution of anthropogenic activities (trade) in this almost global spread. This article contributes further genomic data [...] Read more.

Bacillus anthracis is the etiological agent of the zoonotic disease anthrax. The pathogen has colonized many regions of all inhabited continents. Increasing evidence points to a strong contribution of anthropogenic activities (trade) in this almost global spread. This article contributes further genomic data from 21 B. anthracis strains, including 19 isolated in Germany, aiming to support and detail the human role in anthrax dispersal. The newly sequenced genomes belong to the B. anthracis lineage predominant in China. This lineage is remarkable because of its phylogenetic structure. A polytomy with nine branches radiating from a central node was identified by whole-genome single-nucleotide polymorphism (wgSNP) analysis. Strains from Germany populate two among the nine branches. Detailed analysis of the polytomy indicates that it most likely emerged in China. We propose that the polytomy is the result of the import of contaminated animal products in a limited spatiotemporal frame, followed by the distribution of these products to different locations within China, where new B. anthracis lineages then became independently established. Currently available data point to Bengal as a likely geographic source of the original contamination, and the history of trade exchanges between Bengal and China agrees with the early fifteenth century as a likely time period. The subsequent exports to Germany would have occurred during the 19th century according to German trade history. Notably, Germany has been experiencing localized anthrax outbreaks from this trade heritage up into the 21st century. Full article

(This article belongs to the Special Issue Current Research on Bacillus anthracis Infection)

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18 pages, 324 KB

Open AccessEditor’s ChoiceReview

HSV-1 as a Potential Driver of Alzheimer’s Disease

by Dar-Yin Li, Eun Seok Choi and Xiaoyong Bao

Pathogens 2025, 14(10), 1022; https://doi.org/10.3390/pathogens14101022 - 8 Oct 2025

Cited by 2 | Viewed by 7556

Abstract

Herpes simplex virus type 1 (HSV-1) is a continuous health challenge, and current antiviral treatments cannot cure the virus. As life expectancy continues to increase worldwide, HSV-1 should remain a focus to minimize its associated health complications within the aging population. While often [...] Read more.

Herpes simplex virus type 1 (HSV-1) is a continuous health challenge, and current antiviral treatments cannot cure the virus. As life expectancy continues to increase worldwide, HSV-1 should remain a focus to minimize its associated health complications within the aging population. While often asymptomatic, HSV-1 causes oral and cutaneous lesions and establishes latency with periodic reactivation. Antivirals reduce symptoms but do not eradicate the virus. Emerging evidence links HSV-1 to Alzheimer’s disease (AD) via chronic neuroinflammation, amyloid-beta and tau accumulation, oxidative stress, and synaptic dysfunction, with viral proteins detected in AD-affected brain regions. This review assesses the current evidence for HSV-1 in dementia pathogenesis, examines antiviral strategies as potential neuroprotective interventions, and outlines the experimental models required to establish causality. Full article

(This article belongs to the Section Viral Pathogens)

33 pages, 788 KB

Open AccessEditor’s ChoiceReview

Phage to ESKAPE: Personalizing Therapy for MDR Infections—A Comprehensive Clinical Review

by Andrea Marino, Stefano Stracquadanio, Federica Cosentino, Alberto Enrico Maraolo, Agnese Colpani, Andrea De Vito, Nicholas Geremia, Alice Nicolosi, Alessandra Oliva, Bruno Cacopardo and Giuseppe Nunnari

Pathogens 2025, 14(10), 1011; https://doi.org/10.3390/pathogens14101011 - 7 Oct 2025

Cited by 8 | Viewed by 3984

Abstract

The proliferation of multidrug-resistant (MDR) ESKAPE pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—constitutes a critical global health crisis, rendering conventional antibiotics increasingly ineffective. This comprehensive review evaluates the re-emerging potential of [...] Read more.

The proliferation of multidrug-resistant (MDR) ESKAPE pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—constitutes a critical global health crisis, rendering conventional antibiotics increasingly ineffective. This comprehensive review evaluates the re-emerging potential of bacteriophage therapy as a personalized treatment for infections caused by these organisms. Phages, being viruses that specifically infect and lyse bacteria, offer significant advantages, including high specificity that spares host microbiota, self-replication at the infection site, and potent activity against biofilms. This paper synthesizes current preclinical and clinical evidence, including compassionate-use cases, for phage therapy against each of the ESKAPE pathogens. While case reports and small studies demonstrate considerable success, particularly in salvage therapy for otherwise untreatable infections, significant challenges remain. These include the narrow host range of phages, the potential for bacterial resistance, unpredictable pharmacokinetic and pharmacodynamic parameters, and a complex, non-harmonized regulatory landscape. The review highlights that phage–antibiotic synergy and the use of phage cocktails are promising strategies to overcome some of these limitations. Future progress in phage therapy will depend on standardized manufacturing, robust clinical trials to establish dosing and efficacy, and the development of adaptive regulatory pathways. Phage therapy is positioned not as a replacement for antibiotics but as a vital adjunctive tool in the armamentarium against MDR infections, heralding a move towards a more personalized approach to infectious disease management. Full article

(This article belongs to the Special Issue Classic and Emerging Pathogens as a Cause of Healthcare-Associated Infections: Current Knowledge and Future Approaches)

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13 pages, 3320 KB

Open AccessEditor’s ChoiceArticle

Diversity of Hard Ticks (Acari: Ixodidae) Fauna on Green Habitats of Urban Areas in Eastern Croatia

by Stjepan Krčmar, Petra Matak, Lora Krčmar and Kristina Nikolić

Pathogens 2025, 14(10), 1010; https://doi.org/10.3390/pathogens14101010 - 7 Oct 2025

Cited by 1 | Viewed by 1391

Abstract

Hard ticks (Acari: Ixodidae) are vectors of numerous pathogenic microorganisms in humans and animals. In Croatia, very few studies have been conducted on the diversity of hard tick fauna in urban green areas. Therefore, the aim of this study was to investigate the [...] Read more.

Hard ticks (Acari: Ixodidae) are vectors of numerous pathogenic microorganisms in humans and animals. In Croatia, very few studies have been conducted on the diversity of hard tick fauna in urban green areas. Therefore, the aim of this study was to investigate the diversity and seasonal dynamics of hard tick fauna in three eastern Croatian cities. Three species of ticks were recorded in Osijek and Vukovar, while six species were recorded in the area of the city of Vinkovci. In total, six species were collected during this study, and together with an earlier record of Ixodes canisuga, seven species are now known from urban green habitats in this region. The most abundant species was I. ricinus (82.06%), followed by R. sanguineus s.l. (9.03%), H. concinna (6.51%), D. reticulatus (1.26%), I. hexagonus (0.91%), D. marginatus (0.11%), and I. canisuga (0.11%). The detection of R. sanguineus s.l. in Vinkovci and Vukovar represents the first record of this species in eastern Croatia. In Osijek and Vinkovci, I. ricinus was the most abundant species. This tick is the primary vector of Lyme disease and tick-borne encephalitis, the two most common tick-borne diseases affecting humans in eastern Croatia. In Osijek and Vukovar, peak abundance of ticks was recorded in May, while in Vinkovci in March. Given that the species documented here represent 30.43% of all tick species recorded in Croatia, their presence in urban areas highlights the potential public health risk associated with ticks in these environments. Full article

(This article belongs to the Special Issue Ticks and Tick-Borne Pathogens in the Balkans)

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19 pages, 6403 KB

Open AccessEditor’s ChoiceArticle

Membrane Composition Modulates Vp54 Binding: A Combined Experimental and Computational Study

by Wenhan Guo, Rui Dong, Ayoyinka O. Okedigba, Jason E. Sanchez, Irina V. Agarkova, Elea-Maria Abisamra, Andrew Jelinsky, Wayne Riekhof, Laila Noor, David D. Dunigan, James L. Van Etten, Daniel G. S. Capelluto, Chuan Xiao and Lin Li

Pathogens 2025, 14(10), 1000; https://doi.org/10.3390/pathogens14101000 - 3 Oct 2025

Cited by 1 | Viewed by 1145

Abstract

The recruitment of peripheral membrane proteins is tightly regulated by membrane lipid composition and local electrostatic microenvironments. Our experimental observations revealed that Vp54, a viral matrix protein, exhibited preferential binding to lipid bilayers enriched in anionic lipids such as phosphatidylglycerol (PG) and phosphatidylserine [...] Read more.

The recruitment of peripheral membrane proteins is tightly regulated by membrane lipid composition and local electrostatic microenvironments. Our experimental observations revealed that Vp54, a viral matrix protein, exhibited preferential binding to lipid bilayers enriched in anionic lipids such as phosphatidylglycerol (PG) and phosphatidylserine (PS), compared to neutral phosphatidylcholine/phosphatidylethanolamine liposomes, and this occurred in a curvature-dependent manner. To elucidate the molecular basis of this selective interaction, we performed a series of computational analyses including helical wheel projection, electrostatic potential calculations, electric field lines simulations, and electrostatic force analysis. Our results showed that the membrane-proximal region of Vp54 adopted an amphipathic α-helical structure with a positively charged interface. In membranes containing PG or PS, electrostatic potentials at the interface were significantly more negative, enhancing attraction with Vp54. Field line and force analyses further confirmed that both the presence and spatial clustering of anionic lipids intensify membrane–Vp54 electrostatic interactions. These computational findings align with experimental binding data, jointly demonstrating that membrane lipid composition and organization critically modulate Vp54 recruitment. Together, our findings highlight the importance of electrostatic complementarity and membrane heterogeneity in peripheral protein targeting and provide a framework applicable to broader classes of membrane-binding proteins. Full article

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23 pages, 1105 KB

Open AccessEditor’s ChoiceSystematic Review

Toxoplasmosis in the Era of Targeted Immunotherapy: A Systematic Review of Emerging Cases Linked to Biologics and Small Molecules in Autoimmune Diseases, Oncology and Transplantation

by Stephanie M. Cho, Jose G. Montoya and Despina G. Contopoulos-Ioannidis

Pathogens 2025, 14(10), 1001; https://doi.org/10.3390/pathogens14101001 - 3 Oct 2025

Cited by 2 | Viewed by 2983

Abstract

A systematic review of toxoplasmosis cases in patients receiving targeted immunotherapy with biologics or small molecules was performed. This systematic review searched for case reports, case series and observational studies in PubMed; last search was on 19 July 2025. The review identified 46 [...] Read more.

A systematic review of toxoplasmosis cases in patients receiving targeted immunotherapy with biologics or small molecules was performed. This systematic review searched for case reports, case series and observational studies in PubMed; last search was on 19 July 2025. The review identified 46 toxoplasmosis cases among patients receiving biologics (including CAR T-Cell Therapies) or small molecules for diverse autoimmune, oncologic and transplant conditions. These cases were reported from 18 countries, including the United States and several European countries. Most patients developed severe disease. Fifty percent (23/46) presented with cerebral toxoplasmosis, 33% (15/46) with ocular toxoplasmosis, 7% (3/46) with lymphadenopathy, 4% (2/46) with disseminated disease, 2% (1/46) with both cerebral and ocular disease, 2% (1/46) with pneumonic toxoplasmosis, and 2% (1/46) with severe fetal congenital toxoplasmosis. Among those were also four cases with fatal outcomes due to toxoplasmosis and eight cases with permanent ocular or neurological deficits. In addition, there was a case of fetal congenital toxoplasmosis that occurred despite maternal discontinuation of adalimumab five months before conception, resulting in elective pregnancy termination due to severe fetal cerebral disease. Overall, 44% (20/46) of cases were due to reactivation of chronic latent Toxoplasma infections and 39% (18/46) due to acute primary infections; 17% did not report this information. One case of disseminated acute toxoplasmosis was also identified after eating wild boar sausages, and two cases of severe acute ocular toxoplasmosis after eating undercooked venison meat, and undercooked unspecified type of meat respectively, while on small molecules or biologics. Details on the clinical presentations, management and clinical outcomes of these cases were reported. Recommendations for the management of toxoplasmosis in patients with targeted immunotherapies were also provided. Health care providers should consider toxoplasmosis in patients on biologics or small molecules who present with compatible clinical syndromes. Prompt diagnosis and treatment can be lifesaving. Full article

(This article belongs to the Special Issue Toxoplasmosis in Immunocompromised and Immunocompetent Host: Recent Updates About the Epidemiology, Diagnosis, Clinical Manifestations and Management)

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14 pages, 1552 KB

Open AccessEditor’s ChoiceArticle

Antifungal Activity of 8-Hydroxyquinoline Derivatives Against Candida auris, Candida haemulonii, Cryptococcus neoformans, and Cryptococcus gattii Complex

by Maria Eduarda Krummenauer, Matheus da Silva Camargo, Caroline de Bem Gentz, Marcela Silva Lopes, Letícia Feliciani da Luz, Danielle da Silva Trentin, Belisa Ávila Rodrigues, Karine Rigon Zimmer, Saulo Fernandes de Andrade and Marilene Henning Vainstein

Pathogens 2025, 14(10), 999; https://doi.org/10.3390/pathogens14100999 - 2 Oct 2025

Cited by 3 | Viewed by 1742

Abstract

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both [...] Read more.

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development. Full article

(This article belongs to the Special Issue Emerging Fungal Pathogens and Polymicrobial Infections: Antimicrobial Tolerance, Resistance Mechanisms, and Innovative Therapeutic Approaches)

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19 pages, 2805 KB

Open AccessEditor’s ChoiceArticle

SARS-CoV-2 Infection Influences Wnt/β-Catenin Pathway Components in Astrocytes

by KaReisha F. Robinson, Avantika I. Ahiya, Justin M. Richner and Sarah E. Lutz

Pathogens 2025, 14(10), 994; https://doi.org/10.3390/pathogens14100994 - 2 Oct 2025

Cited by 2 | Viewed by 1657

Abstract

The mechanisms by which SARS-CoV-2 infection lead to neuroinflammation and cognitive impairment in COVID-19 and Long COVID are unclear. Cerebrovascular Wnt/β-catenin pathway activity is suppressed in association with neuroinflammation and cognitive impairment in a mouse model of COVID-19. In this study, we asked [...] Read more.

The mechanisms by which SARS-CoV-2 infection lead to neuroinflammation and cognitive impairment in COVID-19 and Long COVID are unclear. Cerebrovascular Wnt/β-catenin pathway activity is suppressed in association with neuroinflammation and cognitive impairment in a mouse model of COVID-19. In this study, we asked whether SARS-CoV-2 (NY Iota strain) infection of astrocytes would result in cell-autonomous changes in Wnt/β-catenin pathway components. We report that induced pluripotent stem cell (hiPSC)-derived human astrocytes (iAs) are susceptible to sustained infection with SARS-CoV-2 in vitro. Real-time PCR revealed that SARS-CoV-2 infection of iAs decreased transcripts for Wnt3a, Wnt10b, and the downstream pathway effectors β-catenin and TCF3. Wnt7b was increased, as was the proinflammatory chemokine CXCL10. No changes were noted in Wnt3, Wnt7a, TCF1, TCF4, or LEF1. These data indicate that SARS-CoV-2 infection differentially influences Wnt/β-catenin pathway components in astrocytes. These data could have implications for the mechanistic basis of COVID-19 and Long COVID. Full article

(This article belongs to the Section Viral Pathogens)

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19 pages, 4039 KB

Open AccessEditor’s ChoiceReview

Role of Uropathogenic Escherichia coli and Other Pathogens in Kidney Stone Formation: From Pathogenesis to Treatment

by Beata Zalewska-Piątek, Michalina Nagórka and Rafał Piątek

Pathogens 2025, 14(10), 991; https://doi.org/10.3390/pathogens14100991 - 1 Oct 2025

Cited by 4 | Viewed by 3580

Abstract

Urinary tract infections (UTIs) are among the most prevalent infections in the human population. Uropathogenic Escherichia coli, the primary causative agent of UTIs, may also contribute to the development of metabolic kidney stones, particularly those composed of calcium oxalate. Kidney stone disease [...] Read more.

Urinary tract infections (UTIs) are among the most prevalent infections in the human population. Uropathogenic Escherichia coli, the primary causative agent of UTIs, may also contribute to the development of metabolic kidney stones, particularly those composed of calcium oxalate. Kidney stone disease (KSD), known as nephrolithiasis or urolithiasis, is one of the most common disorders of the urinary system. This review explores the significant clinical association between UTIs and kidney stones, focusing on the mechanisms by which UPEC may promote stone formation, including oxidative stress, inflammation, and altered citrate metabolism. It also examines the role of immune responses, particularly macrophage activity, in the progression of KSD. Recent evidence suggests that the composition of the gut microbiota and metabolic imbalances have an additional impact on stone development. In light of these findings, current prevention and treatment strategies, including microbiota-targeted therapies, probiotics, and immune modulation, are also reviewed. Understanding the complex links between UTI, immunity, and metabolism provide new insights into the pathogenesis of KSD and allows for the development of more effective treatments for this disease. Full article

(This article belongs to the Special Issue Pathogenic Escherichia coli: Mechanisms of Virulence, Antimicrobial Resistance and Public Health Implications)

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17 pages, 852 KB

Open AccessEditor’s ChoiceArticle

Coprological and Molecular Analyses of Ruminant Farms in Québec, Canada, Show a Variable Efficacy of Ivermectin Against Gastro-Intestinal Nematodes

by Behrouz Rezanezhad-Dizaji, Levon Abrahamyan, Marjolaine Rousseau and Pablo Godoy

Pathogens 2025, 14(10), 984; https://doi.org/10.3390/pathogens14100984 - 28 Sep 2025

Viewed by 1734

Abstract

Gastro-intestinal nematodes (GINs) are still of great concern in grazing ruminants, such as camelids, ovines and caprines, affecting animal health and productivity. This is mainly due to the development of anthelmintic resistance (AR) to the compounds used long term, without much evaluation on [...] Read more.

Gastro-intestinal nematodes (GINs) are still of great concern in grazing ruminants, such as camelids, ovines and caprines, affecting animal health and productivity. This is mainly due to the development of anthelmintic resistance (AR) to the compounds used long term, without much evaluation on their efficacy, including ivermectin (IVM), the most used anthelmintic drug in livestock. The aims of this study were to determine the efficacy of IVM and identify which GIN species are affecting different ruminant farms in Quebec (QC), Canada. Firstly, we collected fecal samples from six farms with different ruminant species (camelids, goats and sheep) before and after IVM treatment when applicable, analyzing them by Fecal Egg Count (FEC) and further assessments on IVM efficacy through the Fecal Egg Count Reduction Test (FECRT). In addition, molecular analyses were conducted using PCR, targeting the ITS-2 and COX-1 genes to identify GIN species. FECRT was applied only for three farms, showing that variable results with optimal efficacy (ranging from 95.5–100%) were obtained in only one farm, whereas on the other two farms, FECRT exhibited reduced efficacy, suggesting the development of IVM resistance. Among the GIN species found, Haemonchus contortus and Trichostrongylus vitrinus were identified in most of the farms, being present in sheep, goat, llama and alpaca farms, whereas Teladorsagia circumcincta was identified only in sheep and llama samples from four farms but not in alpaca samples. Trichostrongylus axei and Chabertia ovina were present in two farms (sheep and sheep and llamas). Oesophagostomum venulosum was detected in one sheep and one alpaca farm. Only one sheep farm was positive for Trichostrongylus colubriformis and Cooperia curticei. Also, Nematodirus spp. and Trichuris spp. were found in four farms, including sheep and camelids. In addition, three other species were found in camelids, including Camelostrongylus mentulatus (only in the llama samples), whereas Lamanema chavezi and Marshallagia marshalli were identified in one alpaca farm. Therefore, our work reports evidence of an uneven efficacy of IVM against GINs from ruminant farms, including the most likely emergence of IVM resistance. The diversity of GIN species found in ruminant farms in QC along with the inconsistent IVM efficacy are helpful information for veterinarians and animal producers in setting an optimal parasite management programs, including the proper use of IVM and alternative anthelmintic drugs to control these pathogens in grazing livestock. Full article

(This article belongs to the Special Issue Pathogenesis, Epidemiology, and Drug Resistance in Nematode Parasites)

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13 pages, 957 KB

Open AccessEditor’s ChoiceArticle

Food Safety Concerns: Anisakis spp. in Ready-to-Eat Fish from the Greek Market

by Evangelia N. Papapostolou, Serafeim C. Chaintoutis, Panagiota Gousia, Aggeliki Karpouza, Melania Kachrimanidou and Anastasia Diakou

Pathogens 2025, 14(10), 981; https://doi.org/10.3390/pathogens14100981 - 27 Sep 2025

Cited by 2 | Viewed by 3444

Abstract

Nematode parasites of the family Anisakidae can cause human disease when ingested, at the third larval stage (L3), through infected fish or fish products. While human infection is often asymptomatic, in some cases it may present with symptoms ranging from mild to severe [...] Read more.

Nematode parasites of the family Anisakidae can cause human disease when ingested, at the third larval stage (L3), through infected fish or fish products. While human infection is often asymptomatic, in some cases it may present with symptoms ranging from mild to severe gastrointestinal disorders, skin rash, itching, or even anaphylaxis. Ingestion of destroyed L3 (e.g., following processing, sanitisation, or cooking) may still trigger allergic reactions. In the present study, the occurrence of Anisakidae L3 in ready-to-eat (RTE) fish products was investigated. A total of 108 RTE fish products, representing eight species and five processing methods, were examined using (a) macroscopic inspection, (b) artificial digestion (AD), and (c) molecular analysis of both the AD material (to detect non-visible parasite fragments) and the larvae collected by the first two methods. Nematodes morphologically identified as Anisakidae L3 were detected in 32 of the 108 samples (29.62%). Molecular analysis of the AD product did not reveal additional positive samples and confirmed the identification of the isolated larvae as Anisakis simplex sensu stricto and Anisakis pegreffii. Given the public health importance of anisakidosis, the findings of this study provide valuable insight into the prevalence of contamination in RTE fish products currently available on the Greek market. Full article

(This article belongs to the Section Parasitic Pathogens)

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19 pages, 317 KB

Open AccessEditor’s ChoiceReview

Overview of Commercial Vaccines Against Canine Visceral Leishmaniasis: Current Landscape and Future Directions

by Josiane Aparecida Martiniano de Pádua, Diego Ribeiro, Victor Freire Ferreira de Aguilar, Tuane Ferreira Melo, Lilian Lacerda Bueno, Ana Laura Grossi de Oliveira, Ricardo Toshio Fujiwara and Kelly Moura Keller

Pathogens 2025, 14(10), 970; https://doi.org/10.3390/pathogens14100970 - 25 Sep 2025

Cited by 5 | Viewed by 3874

Abstract

Visceral leishmaniasis is a zoonosis commonly caused in Brazil by the parasite Leishmania infantum. This protozoan parasite can infect several species of mammals, with dogs being the main reservoir in urban areas. Several methods are used to prevent the disease, including collars [...] Read more.

Visceral leishmaniasis is a zoonosis commonly caused in Brazil by the parasite Leishmania infantum. This protozoan parasite can infect several species of mammals, with dogs being the main reservoir in urban areas. Several methods are used to prevent the disease, including collars impregnated with 4% deltamethrin to prevent contact between the sandfly and the animal, and vaccines. Vaccines aim to stimulate an immune response that can effectively fight the parasite, with the Th1 immune response being the most desired. There are several research groups around the world dedicated to testing new immunogens against Leishmania spp. and there are currently two commercially available vaccines used to prevent the disease, Neoleish^® and Leti-Fend^®. Leish-Tec^®, a vaccine previously licensed for use in dogs in Brazil, was suspended in May 2023 due to non-compliance in some batches. This also happened with CaniLeish^®, which was discontinued by the European Commission in October 2023. These vaccines have different characteristics that influence their use as a public health measure, and therefore the objective of this review is to describe these immunogens, their characteristics, and their use as a collective prevention measure for canine visceral leishmaniasis. Full article

(This article belongs to the Special Issue Leishmania & Leishmaniasis)

19 pages, 631 KB

Open AccessEditor’s ChoiceReview

Tuberculosis Today: Microbial Insights, Epidemiological Trends, and the Role of Molecular Diagnostics

by Agata Maciejak-Jastrzębska, Grażyna Sygitowicz, Sylwia Brzezińska, Kinga Bielska and Ewa Augustynowicz-Kopeć

Pathogens 2025, 14(10), 965; https://doi.org/10.3390/pathogens14100965 - 24 Sep 2025

Cited by 2 | Viewed by 3193

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a global health problem. One of the characteristic features of mycobacteria is their exceptional resistance to environmental factors and their slow growth rate, both of which significantly prolong microbiological diagnostics. Due to the mortality rate [...] Read more.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a global health problem. One of the characteristic features of mycobacteria is their exceptional resistance to environmental factors and their slow growth rate, both of which significantly prolong microbiological diagnostics. Due to the mortality rate and the rising prevalence of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), early detection and prompt initiation of treatment are extremely important. Traditional diagnostic methods, such as microscopic examination and culture on solid and liquid media, are still important, but are time-consuming and resource-intensive. However, the dynamic development of nucleic acid amplification techniques (NAATs), genotyping assays, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has accelerated the identification of mycobacteria and the detection of drug resistance. Early and precise diagnosis is essential for effective disease control and improved treatment outcomes. This paper reviews the current state of knowledge on tuberculosis; including biological and structural characteristics of mycobacteria; the epidemiology of the disease; and the role of the main diagnostic methods; with a particular focus on molecular methods and MALDI-TOF MS. This paper highlights their advantages and limitations and discusses their implications for the future of TB diagnosis and control Full article

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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 2 | Viewed by 1202

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)

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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 2289

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)

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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 3 | Viewed by 4302

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)

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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 11 | Viewed by 5237

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)

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