Pathogens

25 pages, 1792 KiB

Open AccessEditor’s ChoiceReview

Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria

by Renu Bisht, Pierre D. Charlesworth, Paola Sperandeo and Alessandra Polissi

Pathogens 2024, 13(10), 889; https://doi.org/10.3390/pathogens13100889 - 11 Oct 2024

Cited by 2 | Viewed by 3300

Abstract

Antimicrobial resistance (AMR) has emerged as a global health threat, necessitating immediate actions to develop novel antimicrobial strategies and enforce strong stewardship of existing antibiotics to manage the emergence of drug-resistant strains. This issue is particularly concerning when it comes to Gram-negative bacteria, [...] Read more.

Antimicrobial resistance (AMR) has emerged as a global health threat, necessitating immediate actions to develop novel antimicrobial strategies and enforce strong stewardship of existing antibiotics to manage the emergence of drug-resistant strains. This issue is particularly concerning when it comes to Gram-negative bacteria, which possess an almost impenetrable outer membrane (OM) that acts as a formidable barrier to existing antimicrobial compounds. This OM is an asymmetric structure, composed of various components that confer stability, fluidity, and integrity to the bacterial cell. The maintenance and restoration of membrane integrity are regulated by envelope stress response systems (ESRs), which monitor its assembly and detect damages caused by external insults. Bacterial communities encounter a wide range of environmental niches to which they must respond and adapt for survival, sustenance, and virulence. ESRs play crucial roles in coordinating the expression of virulence factors, adaptive physiological behaviors, and antibiotic resistance determinants. Given their role in regulating bacterial cell physiology and maintaining membrane homeostasis, ESRs present promising targets for drug development. Considering numerous studies highlighting the involvement of ESRs in virulence, antibiotic resistance, and alternative resistance mechanisms in pathogens, this review aims to present these systems as potential drug targets, thereby encouraging further research in this direction. Full article

(This article belongs to the Section Bacterial Pathogens)

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13 pages, 3594 KiB

Open AccessEditor’s ChoiceArticle

‘Candidatus Phytoplasma solani’ Predicted Effector SAP11-like Alters Morphology of Transformed Arabidopsis Plants and Interacts with AtTCP2 and AtTCP4 Plant Transcription Factors

by Marina Drcelic, Andreja Skiljaica, Bruno Polak, Natasa Bauer and Martina Seruga Music

Pathogens 2024, 13(10), 893; https://doi.org/10.3390/pathogens13100893 - 11 Oct 2024

Cited by 3 | Viewed by 1865

Abstract

Phytoplasmas are obligate intracellular pathogens that profoundly modify the development, physiology and behavior of their hosts by secreting effector proteins that disturb signal pathways and interactions both in plant and insect hosts. The characterization of effectors and their host-cell targets was performed for [...] Read more.

Phytoplasmas are obligate intracellular pathogens that profoundly modify the development, physiology and behavior of their hosts by secreting effector proteins that disturb signal pathways and interactions both in plant and insect hosts. The characterization of effectors and their host-cell targets was performed for only a few phytoplasma species where it was shown that the SAP11 effector alters plant morphology by destabilizing plant transcription factors: TEOSINTE BRANCHED 1-CYCLOIDEA-PROLIFERATING CELL FACTOR (TCPs). To explore the possible role of the SAP11-like effector from ‘Ca. P. solani’, we used Arabidopsis thaliana as a model plant. The SAP11-like effector gene from ‘Ca. P. solani’ was introduced into arabidopsis by floral dip and transgenic lines were regenerated. In planta bimolecular fluorescence complementation (BIFC) assays in agroinfiltrated Nicotiana benthamiana leaf cells were conducted to detect interactions between SAP11-like and AtTCP2 and AtTCP4 using confocal microscopy. SAP11-like from ‘Ca. P. solani’ induced significant phenotypic changes in arabidopsis, including crinkled leaves with reduced size, lower biomass, more axillary branches, changes in root morphology, and crinkled and smaller siliques. The BIFC assays proved in planta interaction of SAP11-like effector with AtTCP2 and AtTCP4. To our knowledge, this is the first characterization of the interaction between the ‘Ca. P. solani’ effector and plant transcription factors, suggesting a potential mechanism of modulating plant development and induction of characteristic symptoms in ‘Ca. P. solani’-infected plants. Full article

(This article belongs to the Section Bacterial Pathogens)

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13 pages, 1352 KiB

Open AccessEditor’s ChoiceReview

Immune Modulation by Epstein–Barr Virus Lytic Cycle: Relevance and Implication in Oncogenesis

by Nevena Todorović, Maria Raffaella Ambrosio and Amedeo Amedei

Pathogens 2024, 13(10), 876; https://doi.org/10.3390/pathogens13100876 - 8 Oct 2024

Cited by 1 | Viewed by 3811

Abstract

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it [...] Read more.

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV’s lytic phase contribution to oncogenesis. Full article

(This article belongs to the Special Issue Oncogenic Viruses)

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10 pages, 667 KiB

Open AccessEditor’s ChoiceArticle

Molecular Detection and Characterisation of Coxiella burnetii in Koala (Phascolarctos cinereus) Urogenital Tract Swabs

by Karen O. Mathews, David Phalen, Paul A. Sheehy, Jacqueline M. Norris, Damien P. Higgins and Katrina L. Bosward

Pathogens 2024, 13(10), 873; https://doi.org/10.3390/pathogens13100873 - 4 Oct 2024

Cited by 1 | Viewed by 1858

Abstract

Q fever is a zoonosis caused by Coxiella burnetii, primarily affecting those in close contact with domestic ruminants, the main source of human infection. Coxiella burnetii has also been detected in various wildlife species globally. In Australia, serological and molecular studies have [...] Read more.

Q fever is a zoonosis caused by Coxiella burnetii, primarily affecting those in close contact with domestic ruminants, the main source of human infection. Coxiella burnetii has also been detected in various wildlife species globally. In Australia, serological and molecular studies have shown exposure to and infection by C. burnetii in macropods, bandicoots, and koalas. However, the extent to which these species contribute to human infection remains unclear. An unpublished public health investigation into a Q fever case in a person involved in koala care could not conclusively link the infection to koalas due to the patient’s broad animal exposure. This study aimed to explore the potential role of koalas in transmitting C. burnetii to humans by investigating the presence of C. burnetii DNA in urogenital tract (UGT) swabs from koalas. DNA was extracted from UGT swabs from koalas in three regions in New South Wales, Australia. An optimised multiplex qPCR assay detected C. burnetii DNA in 2 out of 225 samples (0.89%) at approximately 10 genome equivalents per reaction. Both positive samples amplified all three gene targets. MLVA genotyping identified two distinct C. burnetii genotypes previously isolated from Australian Q fever cases. These findings highlight the need for vaccination against Q fever for those in close contact with koalas. Full article

(This article belongs to the Section Bacterial Pathogens)

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17 pages, 4399 KiB

Open AccessEditor’s ChoiceArticle

Development of a One-Step Multiplex qPCR Assay for Detection of Methicillin and Vancomycin Drug Resistance Genes in Antibiotic-Resistant Bacteria

by Jiyoung Lee, Eunyoung Baek, Hyesun Ahn, Jinyoung Bae, Sangha Kim, Sohyeong Kim, Suchan Lee and Sunghyun Kim

Pathogens 2024, 13(10), 853; https://doi.org/10.3390/pathogens13100853 - 30 Sep 2024

Cited by 2 | Viewed by 2761

Abstract

The most common antibiotic-resistant bacteria in Korea are methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Pathogen identification in clinical laboratories can be divided into traditional phenotype- and genotype-based methods, both of which are complementary to each other. The genotype-based method using multiplex [...] Read more.

The most common antibiotic-resistant bacteria in Korea are methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Pathogen identification in clinical laboratories can be divided into traditional phenotype- and genotype-based methods, both of which are complementary to each other. The genotype-based method using multiplex real-time polymerase chain reaction (PCR) is a rapid and accurate technique that analyzes material at the genetic level by targeting genes simultaneously. Accordingly, we aimed to develop a rapid method for studying the genetic characteristics of antibiotic-resistant bacteria and to provide an experimental guide for the efficient antibiotic resistance gene analysis of mecA detection for MRSA and vanA or vanB detection for VRE using a one-step multiplex qPCR assay at an early stage of infection. As a result, the sensitivity and specificity of the mecA gene for clinical S. aureus isolates, including MRSA and methicillin-susceptible S. aureus, were 97.44% (95% CI, 86.82–99.87%) and 96.15% (95% CI, 87.02–99.32%), respectively. The receiver operating characteristic area under the curve for the diagnosis of MRSA was 0.9798 (*** p < 0.0001). Therefore, the molecular diagnostic method using this newly developed one-step multiplex qPCR assay can provide accurate and rapid results for the treatment of patients with MRSA and VRE infections. Full article

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19 pages, 2162 KiB

Open AccessEditor’s ChoiceReview

Molecular Mechanisms of Drug Resistance in Leishmania spp.

by Maria Juliana Moncada-Diaz, Cristian Camilo Rodríguez-Almonacid, Eyson Quiceno-Giraldo, Francis T. H. Khuong, Carlos Muskus and Zemfira N. Karamysheva

Pathogens 2024, 13(10), 835; https://doi.org/10.3390/pathogens13100835 - 27 Sep 2024

Cited by 12 | Viewed by 4434

Abstract

The protozoan parasite Leishmania causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, the severe side effects associated with available therapeutics, and the [...] Read more.

The protozoan parasite Leishmania causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, the severe side effects associated with available therapeutics, and the high rate of treatment failure caused by the parasites’ growing resistance to current medications. In this review, we describe first the common strategies used by pathogens to develop drug resistance and then focus on the arsenal of available drugs to treat leishmaniasis, their modes of action, and the molecular mechanisms contributing to drug resistance in Leishmania spp., including the role of genomic, transcriptional, and translational control. We focus more specifically on our recent discovery of translational reprogramming as a major driver of drug resistance leading to coordinated changes in the translation of transcripts and orchestrating changes in metabolome and lipidome to support drug resistance. A thorough understanding of these mechanisms is essential to identify the key elements needed to combat resistance and improve leishmaniasis treatment methods. Full article

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11 pages, 2551 KiB

Open AccessEditor’s ChoiceArticle

A Novel Jeilongvirus from Florida, USA, Has a Broad Host Cell Tropism Including Human and Non-Human Primate Cells

by Emily DeRuyter, Kuttichantran Subramaniam, Samantha M. Wisely, J. Glenn Morris, Jr. and John A. Lednicky

Pathogens 2024, 13(10), 831; https://doi.org/10.3390/pathogens13100831 - 26 Sep 2024

Cited by 2 | Viewed by 6131

Abstract

A novel jeilongvirus was identified through next-generation sequencing in cell cultures inoculated with spleen and kidney extracts. The spleen and kidney were obtained from a Peromyscus gossypinus rodent (cotton mouse) found dead in the city of Gainesville, in North-Central Florida, USA. Jeilongviruses are [...] Read more.

A novel jeilongvirus was identified through next-generation sequencing in cell cultures inoculated with spleen and kidney extracts. The spleen and kidney were obtained from a Peromyscus gossypinus rodent (cotton mouse) found dead in the city of Gainesville, in North-Central Florida, USA. Jeilongviruses are paramyxoviruses of the subfamily Orthoparamyxovirinae that have been found in bats, cats, and rodents. We designated the virus we discovered as Gainesville rodent jeilong virus 1 (GRJV1). Preliminary results indicate that GRJV1 can complete its life cycle in various human, non-human primate, and rodent cell lines, suggesting that the virus has a generalist nature with the potential for a spillover event. The early detection of endemic viruses circulating within hosts in North-Central Florida can significantly enhance surveillance efforts, thereby bolstering our ability to monitor and respond to potential outbreaks effectively. Full article

(This article belongs to the Section Viral Pathogens)

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10 pages, 1651 KiB

Open AccessEditor’s ChoiceArticle

Virus-Specific Nanobody-Chimeras Degrade the Human Cytomegalovirus US28 Protein in CD34+ Cells

by Emma Poole, Janika Schmitt, Stephen C. Graham, Bernard T. Kelly and John Sinclair

Pathogens 2024, 13(10), 821; https://doi.org/10.3390/pathogens13100821 - 24 Sep 2024

Cited by 1 | Viewed by 1683

Abstract

After primary infection, human cytomegalovirus (HCMV) establishes lifelong persistence, underpinned by latent carriage of the virus with spontaneous reactivation events. In the immune-competent, primary infection or reactivation from latency rarely causes disease. However, HCMV can cause significant disease in immune-compromised individuals such as [...] Read more.

After primary infection, human cytomegalovirus (HCMV) establishes lifelong persistence, underpinned by latent carriage of the virus with spontaneous reactivation events. In the immune-competent, primary infection or reactivation from latency rarely causes disease. However, HCMV can cause significant disease in immune-compromised individuals such as immune-suppressed transplant patients. Latency, where the viral genome is carried in the absence of the production of infectious virions, can be established in undifferentiated cells of the myeloid lineage. A number of stimuli can cause virus reactivation from latency to occur, beginning with the induction of viral immediate-early (IE) lytic gene expression. The suppression of viral IE gene expression to establish and maintain latent infection is known to result from a balance of viral and cellular factors. One key viral factor involved in this is the G protein-coupled receptor US28. Recently, we have shown that US28 is targeted for degradation by a modified nanobody (PCTD-Vun100bv) based on the novel PACTAC (PCSK9-antibody clearance-targeting chimeras) approach for targeted protein degradation. Furthermore, we have shown that this PCTD-Vun100bv-induced degradation of US28 results in IE gene expression in experimentally latently infected CD14+ monocytes. However, HCMV also establishes latency in CD34+ bone marrow cells, the progenitors of CD14+ cells. Here, we show that PCTD-Vun100bv also causes US28 degradation in these CD34+ primary cells, again resulting in the induction of viral IE gene expression. Additionally, we show that PCTD-Vun100bv can target US28 in naturally latently infected CD14+ monocytes from an HCMV-seropositive donor, allowing these latently infected cells to be killed by HCMV-specific cytotoxic T cells from that same donor. These observations support the view that targeting US28 for degradation during natural latency could be a tractable ‘shock-and-kill’ strategy to target the latent HCMV reservoir in myeloid cells. Full article

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

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17 pages, 698 KiB

Open AccessEditor’s ChoiceReview

Gut Microbiota in Patients Receiving Dialysis: A Review

by Xintian Lim, Lijin Ooi, Uzhe Ding, Henry H. L. Wu and Rajkumar Chinnadurai

Pathogens 2024, 13(9), 801; https://doi.org/10.3390/pathogens13090801 - 15 Sep 2024

Cited by 4 | Viewed by 2958

Abstract

The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) [...] Read more.

The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are now increasingly established to result in dysregulation of gut microbiota composition and function. Gut microbiota dysbiosis has been associated with poor clinical outcomes and all-cause mortality in patients with ESKD, particularly individuals receiving dialysis. Prior studies highlighted various factors that affect gut microbiota dysbiosis in CKD and ESKD. These include, but are not limited to, uraemic toxin accumulation, chronic inflammation, immune dysfunction, medications, and dietary restrictions and nutritional status. There is a lack of studies at present that focus on the evaluation of gut microbiota dysbiosis in the context of dialysis. Knowledge on gut microbiota changes in this context is important for determining their impact on dialysis-specific and overall outcomes for this patient cohort. More importantly, evaluating gut microbiota composition can provide information into potential targets for therapeutic intervention. Identification of specific microbial signatures may result in further development of personalised treatments to improve patient outcomes and mitigate complications during dialysis. Optimising gut microbiota through various therapeutic approaches, including dietary adjustments, probiotics, prebiotics, medications, and faecal transplantation, have previously demonstrated potential in multiple medical conditions. It remains to be seen whether these therapeutic approaches are effective within the dialysis setting. Our review aims to evaluate evidence relating to alterations in the gut microbiota of patients undergoing dialysis. A growing body of evidence pointing to the complex yet significant relationship which surrounds gut microbiota and kidney health emphasises the importance of gut microbial balance to improve outcomes for individuals receiving dialysis. Full article

(This article belongs to the Special Issue Molecular Epidemiology of Pathogenic Agents)

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22 pages, 976 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Genomic Analysis of Uropathogenic E. coli: Virulence Factors, Antimicrobial Resistance, and Mobile Genetic Elements

by Kidon Sung, Mohamed Nawaz, Miseon Park, Jungwhan Chon, Saeed A. Khan, Khulud Alotaibi and Ashraf A. Khan

Pathogens 2024, 13(9), 794; https://doi.org/10.3390/pathogens13090794 - 13 Sep 2024

Cited by 3 | Viewed by 2967

Abstract

Our whole-genome sequencing analysis of sixteen uropathogenic E. coli isolates revealed a concerning picture of multidrug resistance and potentially virulent bacteria. All isolates belonged to four distinct clonal groups, with the highly prevalent ST131 lineage being associated with extensive antibiotic resistance and virulence [...] Read more.

Our whole-genome sequencing analysis of sixteen uropathogenic E. coli isolates revealed a concerning picture of multidrug resistance and potentially virulent bacteria. All isolates belonged to four distinct clonal groups, with the highly prevalent ST131 lineage being associated with extensive antibiotic resistance and virulence factors. Notably, all isolates exhibited multidrug resistance, with some resistant to as many as 12 antibiotics. Fluoroquinolone resistance stemmed primarily from efflux pumps and mutations in gyrase and topoisomerase genes. Additionally, we identified genes encoding resistance to extended-spectrum cephalosporins, trimethoprim/sulfamethoxazole, and various heavy metals. The presence of diverse plasmids and phages suggests the potential for horizontal gene transfer and the dissemination of virulence factors. All isolates harbored genomic islands containing virulence factors associated with adhesion, biofilm formation, and invasion. Genes essential for iron acquisition, flagella biosynthesis, secretion systems, and toxin production were also prevalent. Adding further complexity to understanding the isolates’ genetic makeup, we identified CRISPR-Cas systems. This study underscores the need for continued genomic surveillance in understanding the pathogenic mechanisms and resistance profiles of uropathogenic E. coli to aid in developing targeted therapeutic strategies. Full article

(This article belongs to the Special Issue Antimicrobial Resistance of Pathogens Causing Nosocomial Infections)

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18 pages, 4536 KiB

Open AccessEditor’s ChoiceArticle

Molecular Epidemiology of Hepatitis D Virus in the North-East Region of Romania

by Laura Iulia Grecu, Mariana Pavel-Tanasa, Lilia Matei, Camelia Sultana, Simona Maria Ruta, Razvan Ioan Grecu, Ramona Gabriela Ursu, Petru Cianga and Luminita Smaranda Iancu

Pathogens 2024, 13(9), 793; https://doi.org/10.3390/pathogens13090793 - 13 Sep 2024

Cited by 3 | Viewed by 1819

Abstract

The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect [...] Read more.

The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect on hepatocytes and a significant impairment of the host immune response. The HDV genotype largely influences the extent of the pathogenic mechanisms with consequences on disease progression towards cirrhosis, liver decompensation, or hepatocellular carcinoma. In this context, identifying the circulating HDV genotypes in European regions with high prevalence, such as Romania, is crucial for effectively managing the long-term liver health. Here, we report the first comprehensive HDV study in Romania that clinically characterizes 82 patients and performs HDV genotyping by combining the nested-PCR reaction with sequencing analysis in 49 samples with an HDV-RNA load higher than 5000 IU/mL. While all isolates in our study belong to the HDV-1 genotype, the phylogenetic analysis based on sequence data from GenBank reveals the presence of the following potential three groups: (i) Italy and France; (ii) Spain; and (iii) Turkey, Iran, Pakistan, and Germany. This broad clustering highlights the recent surge in migration to and from Western Europe and the Middle East. Equally important, no differences in viral markers, clinical and paraclinical parameters, or treatment options were observed between these identified clusters. Nevertheless, this study considerably advances the understanding of hepatitis D epidemiology and clinical aspects in Romania. Full article

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

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14 pages, 2050 KiB

Open AccessEditor’s ChoiceSystematic Review

“One Health” Perspective on Prevalence of ESKAPE Pathogens in Africa: A Systematic Review and Meta-Analysis

by Ntelekwane George Khasapane, Sebolelo Jane Nkhebenyane, Kgaugelo Lekota, Oriel Thekisoe and Tsepo Ramatla

Pathogens 2024, 13(9), 787; https://doi.org/10.3390/pathogens13090787 - 12 Sep 2024

Cited by 5 | Viewed by 2842

Abstract

The leading cause of hospital-acquired infections worldwide includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) infections. These bacteria are commonly isolated from clinical settings and linked to a number of potentially [...] Read more.

The leading cause of hospital-acquired infections worldwide includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) infections. These bacteria are commonly isolated from clinical settings and linked to a number of potentially fatal diseases associated with hospitals. The objective of this study was to review the prevalence of ESKAPE pathogens in Africa. We gathered and systematically reviewed the literature concerning the prevalence of ESKAPE pathogens, published in the English language from January 2014 to February 2024, from three databases (PubMed, Web of Science and ScienceDirect). Our overall results revealed that S. aureus was the most prevalent species (79.5%), followed by A. baumannii (27.6%), K. pneumoniae (24.2%), Enterobacter spp. (20%), P. aeruginosa (9.0%), and E. faecium (5.1%). Moreover, stool samples had the highest Pooled Prevalence Estimates (PPEs) of 44.0%, followed by urine, nasal, and blood samples with 37.3%, 26.9%, and 22.9%, respectively. For the diagnostic method used to identify these ESKAPE pathogens, VITEK-MS had the highest PPE of 55.2%, followed by whole genome sequencing and PCR with 37.1% and 33.2%, respectively. The highest PPE of ESKAPE pathogens was recorded in West Africa with 77.3%, followed by Central/Middle Africa and East Africa with 43.5% and 25.1%, respectively. The overall PPE of ESKAPE pathogens from humans, animals, the environment (water, soil, and surfaces) and food sources was 35.8%, 37.3%, 47.7%, and 34.2%, respectively. Despite their prevalence in nosocomial settings, studies have shown that the ESKAPE pathogens may be isolated from a range of environmental reservoirs, including soil, dumping sites, beach sand, wastewater, food, and fish farms, among others. This wide source of ESKAPE pathogens substrates indicates the need for a multidisciplinary collaborative partnership for epidemiological studies and intervention efforts by the human, veterinary, and environmental health sectors in Africa. Full article

(This article belongs to the Special Issue One Health: New Approaches, Research and Innovation to Zoonoses)

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11 pages, 556 KiB

Open AccessEditor’s ChoiceArticle

The Occurrence of Chlamydia felis in Cats and Dogs in Hungary

by Áron Balázs Ulbert, Hajnalka Juhász, Zsanett Karácsony, Katalin Bencze, Zoltán Deim, Katalin Burián and Gabriella Terhes

Pathogens 2024, 13(9), 771; https://doi.org/10.3390/pathogens13090771 - 6 Sep 2024

Cited by 1 | Viewed by 2537

Abstract

The World Health Organization (WHO) estimates that many human infections are zoonoses, creating a worldwide public health challenge. Among Chlamydia species, Chlamydia felis is the leading cause of conjunctivitis in cats and is a prominent zoonotic species. This study aimed to determine the [...] Read more.

The World Health Organization (WHO) estimates that many human infections are zoonoses, creating a worldwide public health challenge. Among Chlamydia species, Chlamydia felis is the leading cause of conjunctivitis in cats and is a prominent zoonotic species. This study aimed to determine the occurrence and risk of chlamydiosis in cats and dogs in Szeged, Hungary, and surrounding areas. The total nucleic acids from conjunctival swab samples of symptomatic and asymptomatic animals were extracted using an automated nucleic acid extraction system. After that, DNA was amplified by pan-chlamydia PCR. Bacterial and fungal cultures were also performed to detect other microorganisms. Of the 93 animals, 32 (34.4%) were positive for pan-chlamydia PCR. The positivity rates were 33.3% (26/78) in cats and 40.0% (6/15) in dogs. Furthermore, the positivity rates were 37.2% (16/43) in the cat shelter, 42.4% (14/33) in the veterinary clinic, and 11.7% (2/17) in household pets. In total, 103 species were identified through culture-based examinations, including 97 (94.2%) bacterial and 6 fungal (5.8%) species. From both human and animal health perspectives, it is essential to have a detailed understanding of the circumstances of chlamydiosis, given the global impact of zoonotic diseases. Full article

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17 pages, 2691 KiB

Open AccessEditor’s ChoiceReview

Crimean-Congo Hemorrhagic Fever Virus: An Emerging Threat in Europe with a Focus on Epidemiology in Spain

by María Eslava, Silvia Carlos and Gabriel Reina

Pathogens 2024, 13(9), 770; https://doi.org/10.3390/pathogens13090770 - 6 Sep 2024

Cited by 8 | Viewed by 3891

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease transmitted by ticks of the genus Hyalomma and caused by a virus of the Nairoviridae family. In humans, the virus can generate different clinical presentations that can range from asymptomatic to mild illness or produce [...] Read more.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease transmitted by ticks of the genus Hyalomma and caused by a virus of the Nairoviridae family. In humans, the virus can generate different clinical presentations that can range from asymptomatic to mild illness or produce an hemorrhagic fever with a mortality rate of approximately 30%. The virus pathogenicity and the lack of effective treatment or vaccine for its prevention make it an agent of concern from a public health point of view. The main transmission route is tick bites, so people most exposed to this risk are more likely to become infected. Another risk group are veterinarians and livestock farmers who are in contact with the blood and other fluids of animals that are mostly asymptomatic. Finally, due to its first phase with a non-characteristic symptomatology, there exists a risk of nosocomial infection. It is endemic in Africa, the Balkans, the Middle East, and those Asian countries south of the 50th parallel north, the geographical limit of the main vector. Recently, autochthonous cases have been observed in areas of Europe where the virus was not previously present. Human cases have been detected in Greece, Bulgaria, and Spain. Spain is one of the most affected countries, with a total of 17 autochthonous cases detected since 2013. In other countries, such as France, the virus is present in ticks and animals but has not spread to humans. A high-quality epidemiological surveillance system in these countries is essential to avoid the expansion of this virus to new areas and to limit the impact of current cases. Full article

(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Vector Dynamics, and Pathogenesis)

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29 pages, 1051 KiB

Open AccessEditor’s ChoiceReview

Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies

by Angela Quirino, Nadia Marascio, Francesco Branda, Alessandra Ciccozzi, Chiara Romano, Chiara Locci, Ilenia Azzena, Noemi Pascale, Grazia Pavia, Giovanni Matera, Marco Casu, Daria Sanna, Marta Giovanetti, Giancarlo Ceccarelli, Pierfrancesco Alaimo di Loro, Massimo Ciccozzi, Fabio Scarpa and Antonello Maruotti

Pathogens 2024, 13(9), 766; https://doi.org/10.3390/pathogens13090766 - 5 Sep 2024

Cited by 9 | Viewed by 7009

Abstract

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will [...] Read more.

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage. Full article

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12 pages, 1028 KiB

Open AccessEditor’s ChoiceArticle

Susceptibility of Synanthropic Rodents (Mus musculus, Rattus norvegicus and Rattus rattus) to H5N1 Subtype High Pathogenicity Avian Influenza Viruses

by Tatsufumi Usui, Yukiko Uno, Kazuyuki Tanaka, Tsutomu Tanikawa and Tsuyoshi Yamaguchi

Pathogens 2024, 13(9), 764; https://doi.org/10.3390/pathogens13090764 - 5 Sep 2024

Cited by 2 | Viewed by 3040

Abstract

Synanthropic wild rodents associated with agricultural operations may represent a risk path for transmission of high pathogenicity avian influenza viruses (HPAIVs) from wild birds to poultry birds. However, their susceptibility to HPAIVs remains unclear. In the present study, house mice (Mus musculus [...] Read more.

Synanthropic wild rodents associated with agricultural operations may represent a risk path for transmission of high pathogenicity avian influenza viruses (HPAIVs) from wild birds to poultry birds. However, their susceptibility to HPAIVs remains unclear. In the present study, house mice (Mus musculus), brown rats (Rattus norvegicus), and black rats (Rattus rattus) were experimentally exposed to H5N1 subtype HPAIVs to evaluate their vulnerability to infection. After intranasal inoculation with HA clade 2.2 and 2.3.2.1 H5N1 subtype HPAIVs, wild rodents did not show any clinical signs and survived for 10- and 12-day observation periods. Viruses were isolated from oral swabs for several days after inoculation, while little or no virus was detected in their feces or rectal swabs. In euthanized animals at 3 days post-inoculation, HPAIVs were primarily detected in respiratory tract tissues such as the nasal turbinates, trachea, and lungs. Serum HI antibodies were detected in HA clade 2.2 HPAIV-inoculated rodents. These results strongly suggest that synanthropic wild rodents are susceptible to infection of avian-origin H5N1 subtype HPAIVs and contribute to the virus ecosystem as replication-competent hosts. Detection of infectious viruses in oral swabs indicates that wild rodents exposed to HPAIVs could contaminate food, water, and the environment in poultry houses and play roles in the introduction and spread of HPAIVs in farms. Full article

(This article belongs to the Special Issue Influenza Virus Pathogenesis and Vaccines)

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15 pages, 536 KiB

Open AccessEditor’s ChoiceArticle

Pathogen Prevalence in Cetaceans Stranded along the Italian Coastline between 2015 and 2020

by Carla Grattarola, Guido Pietroluongo, Donatella Belluscio, Enrica Berio, Cristina Canonico, Cinzia Centelleghe, Cristiano Cocumelli, Silvia Crotti, Daniele Denurra, Alessandra Di Donato, Gabriella Di Francesco, Giovanni Di Guardo, Fabio Di Nocera, Ludovica Di Renzo, Stefano Gavaudan, Federica Giorda, Giuseppe Lucifora, Leonardo Marino, Federica Marcer, Letizia Marsili, Sergio Migliore, Ilaria Pascucci, Antonio Petrella, Antonio Pintore, Roberto Puleio, Silva Rubini, Giuliana Terracciano, Anna Toffan, Sandro Mazzariol and Cristina Casalone Show full author list Hide full author list

Pathogens 2024, 13(9), 762; https://doi.org/10.3390/pathogens13090762 - 4 Sep 2024

Cited by 5 | Viewed by 2618

Abstract

The monitoring of stranded marine mammals represents a strategic method to assess their health, conservation status, and ecological role in the marine ecosystem. Networks worldwide track stranding events for the passive monitoring of mortality patterns, emerging and reemerging pathogens, climate change, and environmental [...] Read more.

The monitoring of stranded marine mammals represents a strategic method to assess their health, conservation status, and ecological role in the marine ecosystem. Networks worldwide track stranding events for the passive monitoring of mortality patterns, emerging and reemerging pathogens, climate change, and environmental degradation from a One Health perspective. This study summarizes pathogen prevalence data from the Italian Stranding Network (ISN) derived from post-mortem investigations on cetaceans found dead stranded along the Italian coastline between 2015 and 2020. The decomposition of the carcasses and logistics limited the post-mortem examination to 585 individuals, out of 1236 single-stranding reports. The most relevant pathogens identified were Cetacean Morbillivirus, Herpesvirus, Brucella spp., and Toxoplasma gondii, whose roles as environmental stressors are well known, despite their real impact still needing to be investigated in depth. Statistical analysis showed that age and sex seem to be positively related to the presence of pathogens. This study represents the first step in harmonizing post-mortem investigations, which is crucial for evidence-based conservation efforts. Implementing diagnostic and forensic frameworks could offer an indirect insight into the systematic monitoring of diseases to improve the identification of regional and temporal hotspots in which to target specific mitigation, management, and conservation strategies. Full article

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10 pages, 1356 KiB

Open AccessEditor’s ChoiceArticle

Over-Representation of Torque Teno Mini Virus 9 in a Subgroup of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study

by Karen Giménez-Orenga, Eva Martín-Martínez and Elisa Oltra

Pathogens 2024, 13(9), 751; https://doi.org/10.3390/pathogens13090751 - 1 Sep 2024

Cited by 1 | Viewed by 4358

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder classified by the WHO as postviral fatigue syndrome (ICD-11 8E49 code). Diagnosing ME/CFS, often overlapping with fibromyalgia (FM), is challenging due to nonspecific symptoms and lack of biomarkers. The etiology of ME/CFS and FM [...] Read more.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder classified by the WHO as postviral fatigue syndrome (ICD-11 8E49 code). Diagnosing ME/CFS, often overlapping with fibromyalgia (FM), is challenging due to nonspecific symptoms and lack of biomarkers. The etiology of ME/CFS and FM is poorly understood, but evidence suggests viral infections play a critical role. This study employs microarray technology to quantitate viral RNA levels in immune cells from ME/CFS, FM, or co-diagnosed cases, and healthy controls. The results show significant overexpression of the Torque Teno Mini Virus 9 (TTMV9) in a subgroup of ME/CFS patients which correlate with abnormal HERV and immunological profiles. Increased levels of TTMV9 transcripts accurately discriminate this subgroup of ME/CFS patients from the other study groups, showcasing its potential as biomarker for patient stratification and the need for further research into its role in the disease. Validation of the findings seems granted in extended cohorts by continuation studies. Full article

(This article belongs to the Section Viral Pathogens)

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10 pages, 222 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of 16S-Based Metagenomic NGS as Diagnostic Tool in Different Types of Culture-Negative Infections

by Sara Giordana Rimoldi, Alessandro Tamoni, Alberto Rizzo, Concetta Longobardi, Cristina Pagani, Federica Salari, Caterina Matinato, Chiara Vismara, Gloria Gagliardi, Miriam Cutrera and Maria Rita Gismondo

Pathogens 2024, 13(9), 743; https://doi.org/10.3390/pathogens13090743 - 30 Aug 2024

Cited by 4 | Viewed by 1809

Abstract

Bacterial infections pose significant global health challenges, often underestimated due to difficulties in accurate diagnosis, especially when culture-based diagnostics fail. This study assesses the effectiveness of 16S-based metagenomic next generation sequencing (NGS) for identifying pathogens in culture-negative clinical samples across various medical settings. [...] Read more.

Bacterial infections pose significant global health challenges, often underestimated due to difficulties in accurate diagnosis, especially when culture-based diagnostics fail. This study assesses the effectiveness of 16S-based metagenomic next generation sequencing (NGS) for identifying pathogens in culture-negative clinical samples across various medical settings. Overall, 48% of samples were collected from orthopedics, 15% from neurosurgery, and 12% in cardiac surgery, among others. The detection rate of monomicrobial infections was 68.6%, and 5.7% for polymicrobial infections. In addition, NGS detected bacteria in all samples from the lungs, head and neck, and eye specimens. Cutibacterium acnes (11%, 12/105) was the most frequent microorganism, followed by Staphylococcus epidermidis (10.4%, 11/105), and Staphylococcus aureus (9.5%, 10/105). In conclusion, 16S-targeted metagenomic sequencing enhances pathogen detection capabilities, particularly in instances where traditional cultures fail. By the combination of NGS and bacterial cultures, microbiologists might provide a more accurate diagnosis, guiding more effective treatments and potentially reducing healthcare costs associated with empirical treatments. Full article

(This article belongs to the Special Issue New Insights into Molecular Epidemiology and Diagnostics of Human Pathogens)

10 pages, 1478 KiB

Open AccessEditor’s ChoiceArticle

Spatial Clustering of Rabies by Animal Species in New Jersey, United States, from 1989 to 2023

by Shamim Sarkar and Jaymie R. Meliker

Pathogens 2024, 13(9), 742; https://doi.org/10.3390/pathogens13090742 - 30 Aug 2024

Cited by 1 | Viewed by 1742

Abstract

Identifying spatial clusters of rabies in animals aids policymakers in allocating resources for rabies prevention and control. This study aimed to investigate spatial patterns and hotspots of rabies in different animal species at the county level in New Jersey. Data on animal rabies [...] Read more.

Identifying spatial clusters of rabies in animals aids policymakers in allocating resources for rabies prevention and control. This study aimed to investigate spatial patterns and hotspots of rabies in different animal species at the county level in New Jersey. Data on animal rabies cases from January 1989 to December 2023 were obtained from the New Jersey Department of Health and aggregated by county. Global Moran’s index (I) statistics were computed for each species to detect global spatial clustering (GeoDa version 1.22). Local Moran’s indicators of spatial association (LISA) were computed to identify local clusters of rabies. The results from the LISA analysis were mapped using ArcGIS Pro to pinpoint cluster locations. A total of 9637 rabies cases were analyzed among raccoons (n = 6308), skunks (n = 1225), bats (n = 1072), cats (n = 597), foxes (n = 225), and groundhogs (n = 210). A global Moran’s test indicated significant global spatial clustering in raccoons (I = 0.32, p = 0.012), foxes (I = 0.29, p = 0.011), and groundhogs (I = 0.37, p = 0.005). The LISA results revealed significant spatial clustering of rabies in raccoons and foxes in southeastern New Jersey and in groundhogs in northern New Jersey. These findings could guide the development of targeted oral rabies vaccination programs in high-risk New Jersey counties, reducing rabies exposure among domestic animals and humans. Full article

(This article belongs to the Section Epidemiology of Infectious Diseases)

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12 pages, 768 KiB

Open AccessEditor’s ChoiceArticle

PCR Detection of Bartonella spp. and Borreliella spp. DNA in Dry Blood Spot Samples from Human Patients

by Kerry L. Clark and Shirley Hartman

Pathogens 2024, 13(9), 727; https://doi.org/10.3390/pathogens13090727 - 28 Aug 2024

Viewed by 4924

Abstract

Lyme disease is the most commonly reported vector-borne disease in the United States. Bartonella constitute an additional zoonotic pathogen whose public health impact and diversity continue to emerge. Rapid, sensitive, and specific detection of these and other vector-borne pathogens remains challenging, especially for [...] Read more.

Lyme disease is the most commonly reported vector-borne disease in the United States. Bartonella constitute an additional zoonotic pathogen whose public health impact and diversity continue to emerge. Rapid, sensitive, and specific detection of these and other vector-borne pathogens remains challenging, especially for patients with persistent infections. This report describes an approach for DNA extraction and PCR testing for the detection of Bartonella spp. and Borreliella spp. from dry blood spot (DBS) specimens from human patients. The present study included extraction of DNA and PCR testing of DBS samples from 105 patients with poorly defined, chronic symptoms labeled as Lyme-Like Syndromic Illness (LLSI). Bartonella spp. DNA was detected in 20/105 (19%) and Borreliella spp. DNA was detected in 41/105 (39%) patients with LLSI. Neither group of organisms was detected in DBS samples from 42 healthy control subjects. Bartonella spp. 16S–23S rRNA internal transcribed spacer sequences were highly similar to ones previously identified in yellow flies, lone star ticks, a human patient from Florida, mosquitoes in Europe, or B. apihabitans and choladocola strains from honeybees. These human strains may represent new genetic strains or groups of human pathogenic species of Bartonella. The 41 Borreliella spp. flaB gene sequences obtained from human patients suggested the presence of four different species, including B. burgdorferi, B. americana, B. andersonii, and B. bissettiae/carolinensis-like strains. These results suggest that specific aspects of the DBS DNA extraction and PCR approach enabled the detection of Bartonella spp. and Borreliella spp. DNA from very small amounts of human whole blood from some patients, including specimens stored on filter paper for 17 years. Full article

(This article belongs to the Special Issue The Expanding Clinical Spectrum of Bartonelloses)

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11 pages, 2192 KiB

Open AccessEditor’s ChoiceArticle

Seasonal Patterns of Common Respiratory Viral Infections in Immunocompetent and Immunosuppressed Patients

by Fotis Theodoropoulos, Anika Hüsing, Ulf Dittmer, Karl-Heinz Jöckel, Christian Taube and Olympia E. Anastasiou

Pathogens 2024, 13(8), 704; https://doi.org/10.3390/pathogens13080704 - 20 Aug 2024

Cited by 7 | Viewed by 1702

Abstract

Introduction: Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. Methods: We performed a retrospective analysis of results for 13,591 [...] Read more.

Introduction: Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. Methods: We performed a retrospective analysis of results for 13,591 respiratory tract samples for human metapneumovirus (HMPV), influenza virus, parainfluenza virus (PIV) and respiratory syncytial virus (RSV) in immunocompetent and immunosuppressed patients. A seasonal pattern was aligned to the data of immunocompetent patients through a logistic regression model of positive and negative test results. Results: A narrow seasonal pattern (January to March) was documented for HMPV. Most RSV infections were detected in the winter and early spring months, from December to March, but occasional cases of RSV could be found throughout the year. The peak season for PIV-3 was during the summer months, and that for PIV-4 was mostly in autumn. A narrow seasonal pattern emerged for influenza virus as most infections were detected in the winter, in January and February. The seasonal patterns of HMPV, RSV, PIV, and influenza virus were similar for both immunocompetent and immunocompromised patients. Conclusions: We found no difference in the seasonality of HMPV, RSV, PIV, and influenza virus infections between immunosuppressed and immunocompetent hosts. Full article

(This article belongs to the Special Issue Epidemiology and Clinical Management of Respiratory Viral Diseases, from Children to Adults)

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8 pages, 666 KiB

Open AccessEditor’s ChoiceArticle

Glomerular Injury Is Associated with Severe Courses of Orthohantavirus Infection

by Christian Nusshag, Josephine Uhrig, Gefion Gruber, Pamela Schreiber, Martin Zeier and Ellen Krautkrämer

Pathogens 2024, 13(8), 693; https://doi.org/10.3390/pathogens13080693 - 16 Aug 2024

Cited by 1 | Viewed by 1344

Abstract

Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney [...] Read more.

Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney injury induced by HFRS, we measured specific markers in urine samples of patients with acute Puumala virus (PUUV) infection and determined their correlation with disease severity. Levels of α1-microglobulin (α1-MG) and kidney injury molecule 1 (KIM-1), which is expressed by injured tubular epithelial cells, were measured to detect tubular dysfunction and injury. Immunoglobulin G (IgG) and the podocyte specific protein nephrin served as markers for glomerular injury. All four markers were elevated on admission. Markers of glomerular injury, IgG and nephrin, correlated with markers of disease severity such as length of hospitalization, serum creatinine, and proteinuria. In contrast, tubular injury did not correlate with these severity markers. Our results demonstrate that hantavirus infection induces both glomerular and tubular injury early in the clinical course. However, the glomerular dysfunction and podocyte injury seem to contribute directly to disease severity and to play a more central role in HFRS pathogenicity than direct damage to tubular epithelial cells. Full article

(This article belongs to the Section Viral Pathogens)

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26 pages, 3187 KiB

Open AccessEditor’s ChoiceReview

Aggregatibacter actinomycetemcomitans Dispersin B: The Quintessential Antibiofilm Enzyme

by Jeffrey B. Kaplan, Svetlana A. Sukhishvili, Miloslav Sailer, Khalaf Kridin and Narayanan Ramasubbu

Pathogens 2024, 13(8), 668; https://doi.org/10.3390/pathogens13080668 - 7 Aug 2024

Cited by 11 | Viewed by 4073

Abstract

The extracellular matrix of most bacterial biofilms contains polysaccharides, proteins, and nucleic acids. These biopolymers have been shown to mediate fundamental biofilm-related phenotypes including surface attachment, intercellular adhesion, and biocide resistance. Enzymes that degrade polymeric biofilm matrix components, including glycoside hydrolases, proteases, and [...] Read more.

The extracellular matrix of most bacterial biofilms contains polysaccharides, proteins, and nucleic acids. These biopolymers have been shown to mediate fundamental biofilm-related phenotypes including surface attachment, intercellular adhesion, and biocide resistance. Enzymes that degrade polymeric biofilm matrix components, including glycoside hydrolases, proteases, and nucleases, are useful tools for studying the structure and function of biofilm matrix components and are also being investigated as potential antibiofilm agents for clinical use. Dispersin B is a well-studied, broad-spectrum antibiofilm glycoside hydrolase produced by Aggregatibacter actinomycetemcomitans. Dispersin B degrades poly-N-acetylglucosamine, a biofilm matrix polysaccharide that mediates biofilm formation, stress tolerance, and biocide resistance in numerous Gram-negative and Gram-positive pathogens. Dispersin B has been shown to inhibit biofilm and pellicle formation; detach preformed biofilms; disaggregate bacterial flocs; sensitize preformed biofilms to detachment by enzymes, detergents, and metal chelators; and sensitize preformed biofilms to killing by antiseptics, antibiotics, bacteriophages, macrophages, and predatory bacteria. This review summarizes the results of nearly 100 in vitro and in vivo studies that have been carried out on dispersin B since its discovery 20 years ago. These include investigations into the biological function of the enzyme, its structure and mechanism of action, and its in vitro and in vivo antibiofilm activities against numerous bacterial species. Also discussed are potential clinical applications of dispersin B. Full article

(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans: A D-3 (Dysbiosis, Damage, Disease) Periodontal Pathobiont)

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22 pages, 632 KiB

Open AccessEditor’s ChoiceReview

The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review

by Ami Schattner

Pathogens 2024, 13(8), 667; https://doi.org/10.3390/pathogens13080667 - 7 Aug 2024

Cited by 6 | Viewed by 4370

Abstract

CMV is a ubiquitous DNA virus that establishes infection and results in 40–100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. [...] Read more.

CMV is a ubiquitous DNA virus that establishes infection and results in 40–100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one. Full article

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

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19 pages, 412 KiB

Open AccessEditor’s ChoiceReview

Advancement in Diagnosis, Treatment, and Vaccines against Fasciola hepatica: A Comprehensive Review

by Pablo José Rufino-Moya, Rafael Zafra Leva, Álvaro Martínez-Moreno, Leandro Buffoni, Elora Valderas García, José Pérez Arévalo, Verónica Molina-Hernández, María T. Ruiz-Campillo, Guillem Herrera-Torres and Francisco J. Martínez-Moreno

Pathogens 2024, 13(8), 669; https://doi.org/10.3390/pathogens13080669 - 7 Aug 2024

Cited by 3 | Viewed by 5581

Abstract

In this review article, we aim to provide an overview of fasciolosis in ruminants. Diagnosis through new coprological methods (such as Flukefinder^®, FLOTAC^®, and Mini-FLOTAC^®) remains the most suitable approach for farms. Regarding treatment, there is a [...] Read more.

In this review article, we aim to provide an overview of fasciolosis in ruminants. Diagnosis through new coprological methods (such as Flukefinder^®, FLOTAC^®, and Mini-FLOTAC^®) remains the most suitable approach for farms. Regarding treatment, there is a scarcity of available drugs, and resistance to them has prompted new approaches (including drug combinations, enhanced metabolism, or the use of natural compounds) to address this issue. Additionally, several researchers have developed vaccines to control the disease, but their efficacy varies, and none are currently sufficient for commercial use. Further studies are needed to better understand all aspects discussed in this manuscript, with the goal of improving diagnosis, treatment, and disease control. It is important to note that this manuscript does not delve into in-depth knowledge of the discussed aspects; rather, it provides an overview of the different methodologies related to these three aspects of parasitic disease. Full article

(This article belongs to the Special Issue Veterinary Parasitic Diseases: Advancements in Diagnostics, Therapeutics, and Vaccines)

17 pages, 5094 KiB

Open AccessEditor’s ChoiceArticle

Establishment of a Luciferase-Based Reporter System to Study Aspects of Human Cytomegalovirus Infection, Replication Characteristics, and Antiviral Drug Efficacy

by Julia Tillmanns, Jintawee Kicuntod, Antonia Ehring, Endrit Elbasani, Eva Maria Borst, Debora Obergfäll, Regina Müller, Friedrich Hahn and Manfred Marschall

Pathogens 2024, 13(8), 645; https://doi.org/10.3390/pathogens13080645 - 31 Jul 2024

Cited by 2 | Viewed by 1492

Abstract

Human cytomegalovirus (HCMV) represents a highly medically important pathogen which has constantly been the subject of both molecular and clinical investigations. HCMV infections, especially those in high-risk patients, still raise many unanswered questions, so current investigations are focused on viral pathogenesis, vaccine development, [...] Read more.

Human cytomegalovirus (HCMV) represents a highly medically important pathogen which has constantly been the subject of both molecular and clinical investigations. HCMV infections, especially those in high-risk patients, still raise many unanswered questions, so current investigations are focused on viral pathogenesis, vaccine development, and options for antiviral drug targeting. To this end, the use of suitable viral strains as well as recombinant reporter constructs in cultured cells and model systems has specific significance. We previously reported on the application of various herpesviruses that express green, red, or related fluorescent proteins, especially in the fields of virus–host interaction and antiviral research. Here, we characterized a recombinant version of the clinically relevant and cell type-adaptable HCMV strain TB40, which expresses firefly luciferase as a quantitative reporter of viral replication (TB40-FLuc). The data provide evidence for five main conclusions. First, HCMV TB40-FLuc is employable in multiple settings in primary human cells. Second, viral reporter signals are easily quantifiable, even at early time points within viral replication. Third, the FLuc reporter reflects the kinetics of viral intracellular replication, cascade-like viral IE-E-L protein production, and progeny release. Fourth, as relates to specific applications of the TB40-FLuc system, we demonstrated the reliability of quantitative antiviral compound determination in multi-well formats and its independence from fluorescence-based measurements in the case of autofluorescent inhibitors. Finally, we illustrated increased reporter sensitivity in comparison to other recombinant HCMVs. In essence, recombinant HCMV TB40-FLuc combines several molecular properties that are considered beneficial in studies on viral host tropism, replication efficiency, and antiviral drug assessment. Full article

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

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26 pages, 1432 KiB

Open AccessEditor’s ChoiceReview

Clostridioides difficile and Gut Microbiota: From Colonization to Infection and Treatment

by Patrizia Spigaglia

Pathogens 2024, 13(8), 646; https://doi.org/10.3390/pathogens13080646 - 31 Jul 2024

Cited by 14 | Viewed by 7323

Abstract

Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from [...] Read more.

Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile’s role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota. Full article

(This article belongs to the Special Issue Clostridium Pathogenesis: Virulence, Host Responses, Microbiome, and Interventions)

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14 pages, 3902 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection

by Hernando Gutierrez-Barbosa, Sandra Medina-Moreno, Federico Perdomo-Celis, Harry Davis, Joel V. Chua and Juan C. Zapata

Pathogens 2024, 13(8), 639; https://doi.org/10.3390/pathogens13080639 - 30 Jul 2024

Cited by 2 | Viewed by 2082

Abstract

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, [...] Read more.

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, which exhibit poor hematopoiesis for some cell populations. This study compares three humanized (hu) NOD-derived mouse models for dengue virus-2 (DENV-2) infection in the context of human cytokine expression. Three mouse strains (hu-NSG, hu-EXL, and hu-SGM3) received xenotransplants of human CD34+ fetal cord blood cells from a single donor, and one mouse strain received human peripheral blood mononuclear cells (hu-SGM3-PBMCs). All models exhibited infectious viruses in blood confirmed by plaque assay, but mice expressing human cytokines showed higher viremia compared to conventional NSG mice. The hu-SGM3-PBMCs model developed lethal infections, showing a significant increase in viremia and clinical signs. A detectable human cytokine response was observed in all the DENV-2-infected humanized mouse models. In conclusion, humanized NOD-derived mouse models expressing human cytokines offer a relevant platform for the study of dengue pathogenesis and antiviral therapies. Full article

(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Vector Dynamics, and Pathogenesis)

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12 pages, 1161 KiB

Open AccessEditor’s ChoiceArticle

Investigating the Hepatitis E Virus (HEV) Diversity in Rat Reservoirs from Northern Italy

by Luca De Sabato, Marina Monini, Roberta Galuppi, Filippo Maria Dini, Giovanni Ianiro, Gabriele Vaccari, Fabio Ostanello and Ilaria Di Bartolo

Pathogens 2024, 13(8), 633; https://doi.org/10.3390/pathogens13080633 - 29 Jul 2024

Cited by 3 | Viewed by 2051

Abstract

Hepatitis E virus belonging to the Rocahepevirus ratti species, genotype HEV-C1, has been extensively reported in rats in Europe, Asia and North America. Recently, human cases of hepatitis associated with HEV-C1 infection have been reported, but the zoonotic nature of rat-HEV remains controversial. [...] Read more.

Hepatitis E virus belonging to the Rocahepevirus ratti species, genotype HEV-C1, has been extensively reported in rats in Europe, Asia and North America. Recently, human cases of hepatitis associated with HEV-C1 infection have been reported, but the zoonotic nature of rat-HEV remains controversial. The transmission route of rat-HEV is unidentified and requires further investigation. The HEV strains of the Paslahepevirus balayani species, belonging to the same Hepeviridae family, and including the zoonotic genotype HEV-3 usually found in pigs, have also sporadically been identified in rats. We sampled 115 rats (liver, lung, feces) between 2020 and 2023 in Northeast Italy and the HEV detection was carried out by using Reverse Transcription PCR. HEV RNA was detected in 3/115 (2.6%) rats who tested positive for HEV-C1 strains in paired lung, intestinal contents and liver samples. Overall, none tested positive for the Paslahepevirus balayani strains. In conclusion, our results confirm the presence of HEV-rat in Italy with a prevalence similar to previous studies but show that there is a wide heterogeneity of strains in circulation. The detection of HEV-C1 genotype of Rocahepevirus ratti species in some human cases of acute hepatitis suggests that HEV-C1 may be an underestimated source of human infections. This finding, with the geographically widespread detection of HEV-C1 in rats, raises questions about the role of rats as hosts for both HEV-C1 and HEV-3 and the possibility of zoonotic transmission. Full article

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34 pages, 15774 KiB

Open AccessEditor’s ChoiceReview

Parvoviruses of Aquatic Animals

by Frederick Kibenge, Molly Kibenge, Marco Montes de Oca and Marcos Godoy

Pathogens 2024, 13(8), 625; https://doi.org/10.3390/pathogens13080625 - 26 Jul 2024

Cited by 4 | Viewed by 3213

Abstract

Family Parvoviridae consists of small, non-enveloped viruses with linear, single-stranded DNA genomes of approximately 4-6 kilobases, subdivided into three subfamilies, Parvovirinae, Densovirinae, and Hamaparvovirinae, and unassigned genus Metalloincertoparvovirus. Parvoviruses of aquatic animals infect crustaceans, mollusks, and finfish. This review describes [...] Read more.

Family Parvoviridae consists of small, non-enveloped viruses with linear, single-stranded DNA genomes of approximately 4-6 kilobases, subdivided into three subfamilies, Parvovirinae, Densovirinae, and Hamaparvovirinae, and unassigned genus Metalloincertoparvovirus. Parvoviruses of aquatic animals infect crustaceans, mollusks, and finfish. This review describes these parvoviruses, which are highly host-specific and associated with mass morbidity and mortality in both farmed and wild aquatic animals. They include Cherax quadricarinatus densovirus (CqDV) in freshwater crayfish in Queensland, Australia; sea star-associated densovirus (SSaDV) in sunflower sea star on the Northeastern Pacific Coast; Clinch densovirus 1 in freshwater mussels in the Clinch River, Virginia, and Tennessee, USA, in subfamily Densovirinae; hepatopancreatic parvovirus (HPV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) in farmed shrimp worldwide; Syngnathid ichthamaparvovirus 1 in gulf pipefish in the Gulf of Mexico and parts of South America; tilapia parvovirus (TiPV) in farmed tilapia in China, Thailand, and India, in the subfamily Hamaparvovirinae; and Penaeus monodon metallodensovirus (PmMDV) in Vietnamese P. monodon, in unassigned genus Metalloincertoparvovirus. Also included in the family Parvoviridae are novel parvoviruses detected in both diseased and healthy animals using metagenomic sequencing, such as zander parvovirus from zander in Hungary and salmon parvovirus from sockeye salmon smolts in British Columbia, Canada. Full article

(This article belongs to the Special Issue Virulence Mechanisms, Detection and Control of Aquatic Animal Viruses: 2nd Edition)

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13 pages, 725 KiB

Open AccessEditor’s ChoiceArticle

Multidrug-Resistant Escherichia coli Accumulated by Freshwater Bivalves: An Underestimated Risk for Public Health?

by Joana C. L. Martins, Ana Gonçalves, Conceição Fernandes, Edna Cabecinha, Sandra Monteiro, Hugo Guedes, Gonçalo Almeida, Juliana Garcia, Gabriela J. da Silva, Simone Varandas and Maria J. Saavedra

Pathogens 2024, 13(8), 617; https://doi.org/10.3390/pathogens13080617 - 25 Jul 2024

Cited by 2 | Viewed by 1807

Abstract

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. [...] Read more.

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. Phylogenetic diversity, pathotypic characterization, and antibiotic resistance profiles of E. coli isolated from freshwater bivalves (Anodonta anatina) were assessed. Samples were collected from the Tua River in Northern Portugal, from two different sites, Chelas and Barcel, representing different degrees of contamination. Antimicrobial susceptibility testing was performed by the disk diffusion method, and characterizations of the phylogenetic groups and pathotypes were assessed by PCR-multiplex and real-time PCR-multiplex, respectively. Results showed that 60% of isolates were characterized as MDR, including resistance to carbapenems, considered the last resort against multidrug-resistant bacteria. Within this study, it was also possible to verify the antimicrobial resistance (AMR) profile differences between the two sampling sites, with bivalve isolates from the Chelas site showing a higher percentage of antibiotic resistance. Among the E. coli isolates, the highest prevalence (55%) was observed in group B1, followed by group D or E (15%), group A (10%), and group E or Clade I (10%). None of the isolates were classified as diarrheagenic E. coli (DEC). This work highlights the potential transmission of antimicrobial-resistant bacteria through bivalves in the food chain. The ‘One Health’ approach is crucial for combating antimicrobial resistance, namely in edible freshwater species, emphasizing active surveillance to protect human, animal, and environmental health against the spread of antibiotic-resistant bacteria in aquatic environments. Full article

(This article belongs to the Section Bacterial Pathogens)

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18 pages, 2594 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genomic Analysis of Prophages in Human Vaginal Isolates of Streptococcus agalactiae

by Caitlin S. Wiafe-Kwakye, Andrew Fournier, Hannah Maurais, Katie J. Southworth, Sally D. Molloy and Melody N. Neely

Pathogens 2024, 13(8), 610; https://doi.org/10.3390/pathogens13080610 - 23 Jul 2024

Cited by 1 | Viewed by 2075

Abstract

Prophages, viral genomes integrated into bacterial genomes, are known to enhance bacterial colonization, adaptation, and ecological fitness, providing a better chance for pathogenic bacteria to disseminate and cause infection. Streptococcus agalactiae (Group B Streptococcus or GBS) is a common bacterium found colonizing the [...] Read more.

Prophages, viral genomes integrated into bacterial genomes, are known to enhance bacterial colonization, adaptation, and ecological fitness, providing a better chance for pathogenic bacteria to disseminate and cause infection. Streptococcus agalactiae (Group B Streptococcus or GBS) is a common bacterium found colonizing the genitourinary tract of humans. However, GBS-colonized pregnant women are at risk of passing the organism to the neonate, where it can cause severe infections. GBS typically encode one or more prophages in their genomes, yet their role in pathogen fitness and virulence has not yet been described. Sequencing and bioinformatic analysis of the genomic content of GBS human isolates identified 42 complete prophages present in their genomes. Comparative genomic analyses of the prophage sequences revealed that the prophages could be classified into five distinct clusters based on their genomic content, indicating significant diversity in their genetic makeup. Prophage diversity was also identified across GBS capsule serotypes, sequence types (STs), and clonal clusters (CCs). Comprehensive genomic annotation revealed that all GBS strains encode paratox, a protein that prevents the uptake of DNA in Streptococcus, either on the chromosome, on the prophage, or both, and each prophage genome has at least one toxin-antitoxin system. Full article

(This article belongs to the Section Bacterial Pathogens)

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16 pages, 1969 KiB

Open AccessEditor’s ChoiceReview

Interaction between Intestinal Parasites and the Gut Microbiota: Implications for the Intestinal Immune Response and Host Defence

by Jensine A. Grondin, Asif Jamal, Sadrina Mowna, Tyler Seto and Waliul I. Khan

Pathogens 2024, 13(8), 608; https://doi.org/10.3390/pathogens13080608 - 23 Jul 2024

Cited by 9 | Viewed by 8595

Abstract

Intestinal parasites, including helminths and protozoa, account for a significant portion of the global health burden. The gastrointestinal (GI) tract not only serves as the stage for these parasitic infections but also as the residence for millions of microbes. As the intricacies of [...] Read more.

Intestinal parasites, including helminths and protozoa, account for a significant portion of the global health burden. The gastrointestinal (GI) tract not only serves as the stage for these parasitic infections but also as the residence for millions of microbes. As the intricacies of the GI microbial milieu continue to unfold, it is becoming increasingly apparent that the interactions between host, parasite, and resident microbes help dictate parasite survival and, ultimately, disease outcomes. Across both clinical and experimental models, intestinal parasites have been shown to impact microbial composition and diversity. Reciprocally, microbes can directly influence parasitic survival, colonization and expulsion. The gut microbiota can also indirectly impact parasites through the influence and manipulation of the host. Studying this host–parasite–microbiota axis may help bring about novel therapeutic strategies for intestinal parasitic infection as well as conditions such as inflammatory bowel disease (IBD). In this review, we explore the relationship between intestinal parasites, with a particular focus on common protozoa and helminths, and the gut microbiota, and how these interactions can influence the host defence and intestinal immune response. We will also explore the impact of this tripartite relationship in a clinical setting and its broader implications for human health. Full article

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10 pages, 2282 KiB

Open AccessEditor’s ChoiceArticle

Wolbachia Promotes an Anti-Angiogenic Response Using an In Vitro Model of Vascular Endothelial Cells in Relation to Heartworm Disease

by Manuel Collado-Cuadrado, Claudia Alarcón-Torrecillas, Iván Rodríguez-Escolar, Alfonso Balmori-de la Puente, Elena Infante González-Mohino, Miguel Pericacho and Rodrigo Morchón

Pathogens 2024, 13(7), 603; https://doi.org/10.3390/pathogens13070603 - 22 Jul 2024

Cited by 2 | Viewed by 1499

Abstract

Heartworm disease caused by Dirofilaria immitis is a vector-borne zoonotic disease responsible for the infection of mainly domestic dogs and cats, or these are those for which the most data are known. Humans are an accidental host where a benign, asymptomatic pulmonary nodule [...] Read more.

Heartworm disease caused by Dirofilaria immitis is a vector-borne zoonotic disease responsible for the infection of mainly domestic dogs and cats, or these are those for which the most data are known. Humans are an accidental host where a benign, asymptomatic pulmonary nodule may originate. Dirofilaria immitis also harbours the endosymbiont bacteria of the genus Wolbachia, which play a role in moulting, embryogenesis, inflammatory pathology, and immune response. When Wolbachia sp. is released into the bloodstream, endothelial and pulmonary damage is exacerbated, further encouraging thrombus formation and pulmonary hypertension, facilitating congestive heart failure and death of the animal. Previous studies have shown that parasite excretory/secretory products are able to activate the pro-angiogenic pathway (formation of new vessels) to facilitate parasite survival. The aim of this study was to analyse the role of Wolbachia sp. and its relationship with the cellular processes and the angiogenic pathway in a model of human endothelial cells in vitro. The use of recombinant Wolbachia Surface Protein (rWSP) showed that its stimulation exerted an anti-angiogenic effect by detecting an increase in the production of VEGFR-1/sFlt1 and sEndoglin and did not affect the production of VEGFR-2 and mEndoglin (pro-angiogenic molecules). Furthermore, it did not stimulate cell proliferation or migration, although it did negatively stimulate the formation of pseudocapillaries, slowing down this process. These cellular processes are directly related to the angiogenic pathway so, with these results, we can conclude that Wolbachia sp. is related to the stimulation of the anti-angiogenic pathway, not facilitating the survival of D. immitis in vascular endothelium. Full article

(This article belongs to the Special Issue Dirofilariosis and Angiostrongylosis in Animals and Humans: A Global Challenge)

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16 pages, 2488 KiB

Open AccessEditor’s ChoiceArticle

The Non-Histone Protein FgNhp6 Is Involved in the Regulation of the Development, DON Biosynthesis, and Virulence of Fusarium graminearum

by Jiakuo Cao, Junbo Lv, Limin Zhang, Heng Li, Hao Ma, Yanxiang Zhao and Jinguang Huang

Pathogens 2024, 13(7), 592; https://doi.org/10.3390/pathogens13070592 - 16 Jul 2024

Cited by 2 | Viewed by 1565

Abstract

Fusarium graminearum is the primary causative agent of Fusarium head blight (FHB), a devastating disease affecting cereals globally. The high-mobility group (HMG) of non-histone proteins constitutes vital architectural elements within chromatin, playing diverse roles in various biological processes in eukaryotic cells. Nonetheless, the [...] Read more.

Fusarium graminearum is the primary causative agent of Fusarium head blight (FHB), a devastating disease affecting cereals globally. The high-mobility group (HMG) of non-histone proteins constitutes vital architectural elements within chromatin, playing diverse roles in various biological processes in eukaryotic cells. Nonetheless, the specific functions of HMG proteins in F. graminearum have yet to be elucidated. Here, we identified 10 HMG proteins in F. graminearum and extensively characterized the biological roles of one HMGB protein, FgNhp6. We constructed the FgNhp6 deletion mutant and its complementary strains. With these strains, we confirmed the nuclear localization of FgNhp6 and discovered that the absence of FgNhp6 led to reduced radial growth accompanied by severe pigmentation defects, a significant reduction in conidial production, and a failure to produce perithecia. The ∆FgNhp6 mutant exhibited a markedly reduced pathogenicity on wheat coleoptiles and spikes, coupled with a significant increase in deoxynivalenol production. An RNA sequencing (RNA-seq) analysis indicated that FgNhp6 deletion influenced a wide array of metabolic pathways, particularly affecting several secondary metabolic pathways, such as sterol biosynthesis and aurofusarin biosynthesis. The findings of this study highlight the essential role of FgNhp6 in the regulation of the asexual and sexual reproduction, deoxynivalenol (DON) production, and pathogenicity of F. graminearum. Full article

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31 pages, 4696 KiB

Open AccessEditor’s ChoiceReview

Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape

by Wenlong An, Simran Lakhina, Jessica Leong, Kartik Rawat and Matloob Husain

Pathogens 2024, 13(7), 561; https://doi.org/10.3390/pathogens13070561 - 3 Jul 2024

Cited by 11 | Viewed by 6727

Abstract

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. Influenza virus causes an acute respiratory disease, commonly known as the “flu” in humans. In some individuals, flu can lead to pneumonia and acute respiratory distress syndrome. Influenza A virus (IAV) [...] Read more.

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. Influenza virus causes an acute respiratory disease, commonly known as the “flu” in humans. In some individuals, flu can lead to pneumonia and acute respiratory distress syndrome. Influenza A virus (IAV) is the most significant because it causes recurring seasonal epidemics, occasional pandemics, and zoonotic outbreaks in human populations, globally. The host innate immune response to IAV infection plays a critical role in sensing, preventing, and clearing the infection as well as in flu disease pathology. Host cells sense IAV infection through multiple receptors and mechanisms, which culminate in the induction of a concerted innate antiviral response and the creation of an antiviral state, which inhibits and clears the infection from host cells. However, IAV antagonizes and escapes many steps of the innate antiviral response by different mechanisms. Herein, we review those host and viral mechanisms. This review covers most aspects of the host innate immune response, i.e., (1) the sensing of incoming virus particles, (2) the activation of downstream innate antiviral signaling pathways, (3) the expression of interferon-stimulated genes, (4) and viral antagonism and escape. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses, 2nd Edition)

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24 pages, 3727 KiB

Open AccessEditor’s ChoiceReview

Zika Virus Neuropathogenesis—Research and Understanding

by Anna D. Metzler and Hengli Tang

Pathogens 2024, 13(7), 555; https://doi.org/10.3390/pathogens13070555 - 2 Jul 2024

Cited by 4 | Viewed by 5875

Abstract

Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV—neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem [...] Read more.

Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV—neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem cells) and non-neuronal cells (primary fibroblasts, epidermal keratinocytes, dendritic cells, monocytes, macrophages, and Sertoli cells)—displays its own characteristic changes to their cell physiology and has various impacts on disease. Here, we provide an in-depth review of the ZIKV life cycle and its cellular targets, and discuss the current knowledge of how infections cause neuropathologies, as well as what approaches researchers are currently taking to further advance such knowledge. A key aspect of ZIKV neuropathogenesis is virus-induced neuronal apoptosis via numerous mechanisms including cell cycle dysregulation, mitochondrial fragmentation, ER stress, and the unfolded protein response. These, in turn, result in the activation of p53-mediated intrinsic cell death pathways. A full spectrum of infection models including stem cells and co-cultures, transwells to simulate blood–tissue barriers, brain-region-specific organoids, and animal models have been developed for ZIKV research. Full article

(This article belongs to the Special Issue Neuropathogenesis of Arboviruses)

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8 pages, 366 KiB

Open AccessEditor’s ChoiceReview

High HTLV-1 Proviral Load Predates and Predicts HTLV-1-Associated Disease: Literature Review and the London Experience

by Graham P. Taylor, William Evans and Carolina Rosadas

Pathogens 2024, 13(7), 553; https://doi.org/10.3390/pathogens13070553 - 1 Jul 2024

Cited by 4 | Viewed by 2356

Abstract

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood [...] Read more.

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases. Full article

(This article belongs to the Special Issue Viral Infections of Humans: Epidemiology and Control)

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20 pages, 1978 KiB

Open AccessEditor’s ChoiceArticle

Water Stress and Black Cutworm Feeding Modulate Plant Response in Maize Colonized by Metarhizium robertsii

by Imtiaz Ahmad, Maria del Mar Jimenez-Gasco and Mary E. Barbercheck

Pathogens 2024, 13(7), 544; https://doi.org/10.3390/pathogens13070544 - 27 Jun 2024

Cited by 2 | Viewed by 1603

Abstract

Plants face many environmental challenges and have evolved different strategies to defend against stress. One strategy is the establishment of mutualistic associations with endophytic microorganisms which contribute to plant defense and promote plant growth. The fungal entomopathogen Metarhizium robertsii is also an endophyte [...] Read more.

Plants face many environmental challenges and have evolved different strategies to defend against stress. One strategy is the establishment of mutualistic associations with endophytic microorganisms which contribute to plant defense and promote plant growth. The fungal entomopathogen Metarhizium robertsii is also an endophyte that can provide plant-protective and growth-promoting benefits to the host plant. We conducted a greenhouse experiment in which we imposed stress from deficit and excess soil moisture and feeding by larval black cutworm (BCW), Agrotis ipsilon, to maize plants that were either inoculated or not inoculated with M. robertsii (Mr). We evaluated plant growth and defense indicators to determine the effects of the interaction between Mr, maize, BCW feeding, and water stress. There was a significant effect of water treatment, but no effect of Mr treatment, on plant chlorophyl, height, and dry biomass. There was no effect of water or Mr treatment on damage caused by BCW feeding. There was a significant effect of water treatment, but not Mr treatment, on the expression of bx7 and rip2 genes and on foliar content of abscisic acid (ABA), 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and gibberellin 19 (GA19), whereas GA53 was modulated by Mr treatment. Foliar content of GA19 and cis-Zeatin (cZ) was modulated by BCW feeding. In a redundancy analysis, plant phenology, plant nutrient content, and foliar DIMBOA and ABA content were most closely associated with water treatments. This study contributes toward understanding the sophisticated stress response signaling and endophytic mutualisms in crops. Full article

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19 pages, 3407 KiB

Open AccessEditor’s ChoiceSystematic Review

Difference in the Intestinal Microbiota between Breastfeed Infants and Infants Fed with Artificial Milk: A Systematic Review

by Francesco Inchingolo, Angelo Michele Inchingolo, Giulia Latini, Laura Ferrante, Elisabetta de Ruvo, Merigrazia Campanelli, Marialuisa Longo, Andrea Palermo, Alessio Danilo Inchingolo and Gianna Dipalma

Pathogens 2024, 13(7), 533; https://doi.org/10.3390/pathogens13070533 - 24 Jun 2024

Cited by 17 | Viewed by 5698

Abstract

The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed [...] Read more.

The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed infants with that of F-fed infants and to evaluate the clinical implications of these differences. We searched databases on Scopus, Web of Science, and Pubmed with the following keywords: “gut microbiota”, “gut microbiome”, and “neonatal milk”. The inclusion criteria were articles relating to the analysis of the intestinal microbiome of newborns in relation to the type of nutrition, clinical studies or case series, excluding reviews, meta-analyses, animal models, and in vitro studies. The screening phase ended with the selection of 13 publications for this work. Breastfed infants showed higher levels of beneficial bacteria such as Bifidobacterium and Lactobacillus, while F-fed infants had a higher prevalence of potentially pathogenic bacteria, including Clostridium difficile and Enterobacteriaceae. Infant feeding type influences the composition of oral GM significantly. Breastfeeding promotes a healthier and more diverse microbial ecosystem, which may offer protective health benefits. Future research should explore strategies to improve the GM of F-fed infants and understand the long-term health implications. Full article

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

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12 pages, 255 KiB

Open AccessEditor’s ChoiceArticle

Prevalence of Subgingival Aggregatibacter actinomycetemcomitans: Descriptive Cross-Sectional Study

by Nabil Khzam, Omar Kujan, Dorte Haubek, Aysen Arslan, Anders Johansson, Jan Oscarsson, Zeinab Razooqi and Leticia Algarves Miranda

Pathogens 2024, 13(7), 531; https://doi.org/10.3390/pathogens13070531 - 24 Jun 2024

Cited by 5 | Viewed by 2008

Abstract

This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. [...] Read more.

This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. The identification of A. actinomycetemcomitans was performed using quantitative polymerase chain reaction. A descriptive analysis, a chi-square test, and a binary logistic regression statistical evaluation were performed. The prevalence of A. actinomycetemcomitans in this population of 156 participants was 17.30% (27 patients). The prevalence of stage-III periodontitis was 75.6% and greater in older men, while the prevalence of stage-IV periodontitis was 22.4% and greater in younger women. We observed a significant relation between the risk of severe periodontitis (stage-IV) and poor oral hygiene (p = 0.006), attendance at dental appointments (p ≤ 0.001), and familial history of periodontitis (p = 0.032). In conclusion, twenty-seven individuals were positive for A. actinomycetemcomitans. Poor oral hygiene, family history of periodontitis, and irregular attendance at dental appointments were identified as potential risk factors for severe periodontitis in this cohort. Full article

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

16 pages, 14810 KiB

Open AccessEditor’s ChoiceArticle

Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice

by Soo-Jin Oh, Pratima Kumari, Tabassum Tasnim Auroni, Shannon Stone, Heather Pathak, Amany Elsharkawy, Janhavi Prasad Natekar, Ok Sarah Shin and Mukesh Kumar

Pathogens 2024, 13(7), 528; https://doi.org/10.3390/pathogens13070528 - 22 Jun 2024

Cited by 5 | Viewed by 2490

Abstract

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this [...] Read more.

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this study was to gain insights into the molecular pathogenesis of neurological manifestations in this mouse model. To analyze differentially expressed genes (DEGs) in the brains of mice following SARS-CoV-2 infection, we performed NanoString gene expression analysis using three individual animal samples at 1, 3, and 6 days post-infection. We identified the DEGs by comparing them to animals that were not infected with the virus. We found that genes upregulated at day 6 post-infection were mainly associated with Toll-like receptor (TLR) signaling, RIG-I-like receptor (RLR) signaling, and cell death pathways. However, downregulated genes were associated with neurodegeneration and synaptic signaling pathways. In correlation with gene expression profiles, a multiplexed immunoassay showed the upregulation of multiple cytokines and chemokines involved in inflammation and cell death in SARS-CoV-2-infected brains. Furthermore, the pathway analysis of DEGs indicated a possible link between TLR2-mediated signaling pathways and neuroinflammation, as well as pyroptosis and necroptosis in the brain. In conclusion, our work demonstrates neuroinflammation-associated gene expression profiles, which can provide key insight into the severe disease observed in COVID-19 patients. Full article

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26 pages, 1057 KiB

Open AccessEditor’s ChoiceReview

Advances in Laboratory Diagnosis of Coronavirus Infections in Cattle

by Shaun van den Hurk, Girija Regmi, Hemant K. Naikare and Binu T. Velayudhan

Pathogens 2024, 13(7), 524; https://doi.org/10.3390/pathogens13070524 - 21 Jun 2024

Cited by 4 | Viewed by 2727

Abstract

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle: a respiratory form and a gastrointestinal form. All age groups of cattle are affected by the [...] Read more.

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle: a respiratory form and a gastrointestinal form. All age groups of cattle are affected by the respiratory form of coronavirus, whereas the gastroenteric form causes neonatal diarrhea or calf scours in young cattle and winter dysentery in adult cattle. The tremendous impacts of bovine respiratory disease and the associated losses are well-documented and underscore the importance of this pathogen. Beyond this, studies have demonstrated significant impacts on milk production associated with outbreaks of winter dysentery, with up to a 30% decrease in milk yield. In North America, BCoV was identified for the first time in 1972, and it continues to be a significant economic concern for the cattle industry. A number of conventional and molecular diagnostic assays are available for the detection of BCoV from clinical samples. Conventional assays for BCoV detection include virus isolation, which is challenging from clinical samples, electron microscopy, fluorescent antibody assays, and various immunoassays. Molecular tests are mainly based on nucleic acid detection and predominantly include conventional and real-time polymerase chain reaction (PCR) assays. Isothermal amplification assays and genome sequencing have gained increased interest in recent years for the detection, characterization, and identification of BCoV. It is believed that isothermal amplification assays, such as loop-mediated isothermal amplification and recombinase polymerase amplification, among others, could aid the development of barn-side point-of-care tests for BCoV. The present study reviewed the literature on coronavirus infections in cattle from the last three and a half decades and presents information mainly on the current and advancing diagnostics in addition to epidemiology, clinical presentations, and the impact of the disease on the cattle industry. Full article

(This article belongs to the Special Issue Diagnostics of Emerging and Re-Emerging Pathogens)

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13 pages, 1607 KiB

Open AccessEditor’s ChoiceArticle

Humoral Immune Response in Immunized Sheep with Bovine Coronavirus Glycoproteins Delivered via an Adenoviral Vector

by Annamaria Pratelli, Paolo Capozza, Sergio Minesso, Maria Stella Lucente, Francesco Pellegrini, Maria Tempesta, Valentina Franceschi, Canio Buonavoglia and Gaetano Donofrio

Pathogens 2024, 13(7), 523; https://doi.org/10.3390/pathogens13070523 - 21 Jun 2024

Cited by 5 | Viewed by 1476

Abstract

Bovine coronavirus (BCoV) is distributed globally and mainly causes different clinical manifestations: enteric diarrhea in calves, winter dysentery in adults, and respiratory symptoms in cattle of all ages. Low mortality and high morbidity are the hallmarks of BCoV infection, usually associated with substantial [...] Read more.

Bovine coronavirus (BCoV) is distributed globally and mainly causes different clinical manifestations: enteric diarrhea in calves, winter dysentery in adults, and respiratory symptoms in cattle of all ages. Low mortality and high morbidity are the hallmarks of BCoV infection, usually associated with substantial economic losses for the livestock industry. Vaccination, combined with the implementation of biosecurity measures, is the key strategy for the prevention of infections. This pilot study evaluates the immunogenicity of a recombinant vaccine containing two BCoV antigens (S and M) in sheep, compared to vaccines containing only the M or S protein. Three groups of sheep were inoculated intramuscularly at day 0 and day 21 with recombinant adenoviruses expressing BCoV S protein (AdV-BCoV-S), BCoV M protein (AdV-BCoV-M), or both proteins (AdV-BCoV-S + M). Serum antibodies were evaluated using immunofluorescence (IF) and serum neutralization (SN) tests. Moderate seroconversion was observed by day 21, but serum antibodies detected via SN increased from 1:27.5 (day 21) to 1:90 (day 28) in sheep inoculated with the recombinant AdV expressing both the S- and M-BCoV proteins. Based on the SN results, a repeated-measures ANOVA test indicated a more significant difference in immune response between the three groups (F = 20.47; p < 0.001). The experimental investigation produced satisfactory results, highlighting that the S + M recombinant vaccine was immunogenic, stimulating a valid immune response. Despite some inherent limitations, including a small sample size and the absence of challenge tests, the study demonstrated the efficacy of the immune response induced via the recombinant vaccine containing both S and M proteins compared to that induced via the individual proteins S or M. Full article

(This article belongs to the Section Vaccines and Therapeutic Developments)

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12 pages, 1721 KiB

Open AccessEditor’s ChoiceArticle

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity

by Tatevik Antonyan, Garri Chilingaryan, Karen Zagorski, Manush Ghazaryan, Armine Hovakimyan, Hayk Davtyan, Irina Petrushina, Olga King, Roman Kniazev, Nikolai Petrovsky and Anahit Ghochikyan

Pathogens 2024, 13(6), 520; https://doi.org/10.3390/pathogens13060520 - 20 Jun 2024

Cited by 1 | Viewed by 1876

Abstract

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the [...] Read more.

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates. We prepared and characterized 18 vaccines incorporating small peptide fragments from SARS-CoV-2 Spike protein fused with the MultiTEP sequence using overlapping PCR. Wild-type mice were immunized intramuscularly with the immunogen formulated in AdvaxCpG adjuvant. Serum antibodies were detected by ELISA, surrogate neutralization, and pseudovirus neutralization assays. Finally, the most promising vaccine candidate was administered to three non-human primates. All vaccines generated high titers of spike-binding IgG antibodies. However, only three vaccines generated antibodies that blocked RBD binding to the ACE2 receptor in a surrogate virus neutralization assay. However, none of the vaccines induced antibodies able to neutralize pseudotype viruses, including after the administration of the lead vaccine to NHPs. MultiTEP-based COVID-19 vaccines elicited robust, IgG-binding responses against the Spike protein in mice and non-human primates, but these antibodies were not neutralizing, underscoring the need to refine this approach further. Full article

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12 pages, 1504 KiB

Open AccessEditor’s ChoiceArticle

Differential Gene Expression in the Upper Respiratory Tract following Acute COVID-19 Infection in Ambulatory Patients That Develop Long COVID

by Mia J. Biondi, Mary Addo, Muhammad Atif Zahoor, Elsa Salvant, Paul Yip, Bethany Barber, David Smookler, Sumaiyah Wasif, Kayla Gaete, Christopher Kandel, Jordan J. Feld, Hubert Tsui and Robert A. Kozak

Pathogens 2024, 13(6), 510; https://doi.org/10.3390/pathogens13060510 - 17 Jun 2024

Cited by 1 | Viewed by 3237

Abstract

Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the [...] Read more.

Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens. Full article

(This article belongs to the Section Viral Pathogens)

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13 pages, 1980 KiB

Open AccessEditor’s ChoiceArticle

Prevalence and Control of Pseudomonas aeruginosa in Tourist Facilities across the Canary Islands, Spain

by Antonio Doménech-Sánchez, Elena Laso and Sebastián Albertí

Pathogens 2024, 13(6), 501; https://doi.org/10.3390/pathogens13060501 - 12 Jun 2024

Viewed by 1875

Abstract

Pseudomonas aeruginosa is a common pathogen associated with recreational water facilities and poses risks to public health. However, data on the prevalence of P. aeruginosa in tourist destinations like the Canary Islands, Spain, remain limited. We assessed P. aeruginosa prevalence in 23 tourist [...] Read more.

Pseudomonas aeruginosa is a common pathogen associated with recreational water facilities and poses risks to public health. However, data on the prevalence of P. aeruginosa in tourist destinations like the Canary Islands, Spain, remain limited. We assessed P. aeruginosa prevalence in 23 tourist facilities from 2016 to 2019. Compliance with water quality standards was evaluated, and 3962 samples were collected and analyzed. We examined different types of recreational water installations, including outer swimming pools, whirlpools, and cold wells. Of the sampled facilities, 31.2% did not comply with the current legislation’s parametric values, mainly due to inadequate disinfectant levels, water temperature, and P. aeruginosa presence. The prevalence of P. aeruginosa was 4.8%, comparable to some European countries but lower than others. Cold wells displayed the highest non-compliance rate (89.2%) and yet exhibited a lower P. aeruginosa prevalence (1.9%) than outer swimming pools and whirlpools. Children’s presence did not significantly impact P. aeruginosa contamination. Chlorine-based disinfectants are more effective than bromine-based ones in controlling P. aeruginosa. Regional variability in contamination was observed, with Fuerteventura showing lower colonization rates. Disinfectant levels play a critical role in P. aeruginosa control, and maintaining adequate levels is essential, particularly in bromine-treated installations. Our findings provide valuable insights into the prevalence and distribution of P. aeruginosa in recreational waters within tourist facilities. Tailored strategies are needed to ensure water safety in different Spanish regions. Continued monitoring and assessment, combined with artificial intelligence and machine learning, will enable the implementation of targeted interventions to protect the health of recreational water users. Full article

(This article belongs to the Section Bacterial Pathogens)

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31 pages, 4290 KiB

Open AccessEditor’s ChoiceReview

Brief Insights into mRNA Vaccines: Their Successful Production and Nanoformulation for Effective Response against COVID-19 and Their Potential Success for Influenza A and B

by Amerah Parveen and Amal Ali Elkordy

Pathogens 2024, 13(6), 500; https://doi.org/10.3390/pathogens13060500 - 12 Jun 2024

Cited by 4 | Viewed by 4002

Abstract

A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune cells, which are produced because of antigen-encoding mRNA translation, a protein. For example, COVID-19 mRNA vaccines produce the spike protein [...] Read more.

A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune cells, which are produced because of antigen-encoding mRNA translation, a protein. For example, COVID-19 mRNA vaccines produce the spike protein of the COVID-19 virus, whereas for influenza virus, mRNA vaccines target the haemagglutinin protein to treat the flu, and it requires modifications depending on the pandemic or seasonal viruses as it is capable of adapting the immune response, which makes the development of vaccines arduous. The protein molecule promotes an adaptive immune response that eliminates and terminates the corresponding virus or pathogen. There are many challenges to delivering an mRNA vaccine into the body; hence, the encapsulation of the mRNA (usually within lipid nanoparticles) is necessary to protect the mRNA from the body’s surrounding environment. In this review article, we focus mainly on the production, formulation, and stabilization of mRNA vaccines in general, elaborating more on and focusing more on SARS-CoV-2, or COVID-19, and influenza viruses, which have become a major concern as these viruses have turned into life-threatening diseases. Full article

(This article belongs to the Special Issue Advance in Influenza A and Influenza B Viruses)

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15 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

Cytomegalovirus, Epstein-Barr Virus, Herpes Simplex Virus, and Varicella Zoster Virus Infection Dynamics in People with Multiple Sclerosis from Northern Italy

by Peter A. Maple, Radu Tanasescu, Cris S. Constantinescu, Paola Valentino, Marco Capobianco, Silvia D’Orso, Giovanna Borsellino, Luca Battistini, Giovanni Ristori, Rosella Mechelli, Marco Salvetti and Bruno Gran

Pathogens 2024, 13(6), 499; https://doi.org/10.3390/pathogens13060499 - 12 Jun 2024

Cited by 1 | Viewed by 2706

Abstract

Previous exposure to Epstein–Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with [...] Read more.

Previous exposure to Epstein–Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with MS in an Italian population. Serum samples (n = 200) from Italian people with multiple sclerosis (PwMS) classified as the relapsing-and-remitting clinical phenotype and (n = 137) healthy controls (HCs) were obtained from the CRESM Biobank, Orbassano, Italy. Both PwMS and HCs samples were selected according to age group (20–39 years, and 40 or more years) and sex. EBV virus capsid antigen (VCA) IgG, EBV nucleic acid-1 antigen (EBNA-1) IgG, CMV IgG, herpes simplex virus (HSV) IgG, and varicella zoster virus (VZV) IgG testing was undertaken using commercial ELISAs. EBV VCA IgG and EBNA-1 IgG seroprevalences were 100% in PwMS and 93.4% and 92.4%, respectively, in HCs. EBV VCA IgG and EBNA-1 IgG levels were higher (p < 0.001) in PwMS compared with HCs. For PwMS, the EBNA-1 IgG levels decreased with age, particularly in females. The CMV IgG seroprevalence was 58.7% in PwMS and 62.9% in HCs. CMV IgG seroprevalence increased with age. The HSV IgG seroprevalence was 71.2% in PwMS and 70.8% in HCs. HSV IgG levels were lower (p = 0.0005) in PwMS compared with HCs. VZV IgG seroprevalence was 97.5% in PwMS and 98.5% in HCs. In the population studied, several herpesvirus infections markers may have been influenced by the age and sex of the groups studied. The lack of a negative association of MS with CMV infection, and the observation of lower levels of HSV IgG in PwMS compared with HCs are findings worthy of further investigation. Full article

(This article belongs to the Special Issue Viral Infections and Their Effects on the Central Nervous System (CNS))

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