Pathogens

24 pages, 2259 KB

Open AccessSystematic Review

The Role of Microbiota and Fecal Transplantation in Inflammatory Bowel Disease

by Isabel Lagos, Edith Pérez de Arce, Ilaria Faggiani, Ferdinando D’Amico, Alessandra Zilli, Federica Furfaro, Sara Massironi, Clelia Cicerone, Virginia Solitano, Tommaso Lorenzo Parigi, Laurent Peyrin-Biroulet, Silvio Danese and Mariangela Allocca

Pathogens 2026, 15(4), 451; https://doi.org/10.3390/pathogens15040451 - 21 Apr 2026

Viewed by 767

Abstract

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and [...] Read more.

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and therapeutic modulation. We conducted a systematic review to synthesize current evidence on microbiota alterations in IBD and the clinical application of fecal microbiota transplantation (FMT). A total of 118 studies were included (76 focused on microbiota profiling and 42 evaluated FMT as therapy). Across heterogeneous study designs and microbial characterization methods, reduced microbial diversity was the most consistently reported alteration, generally more pronounced in CD than in UC. Depletion of Faecalibacterium prausnitzii—a key butyrate producer with anti-inflammatory properties—was commonly reported, often accompanied by functional impairment in short-chain fatty acid production. Microbial patterns were frequently associated with mucosal inflammation and varied across disease phenotypes; these patterns have been increasingly explored as predictors of treatment response and relapse, although mechanistic interpretation remains limited and causal relationships are difficult to establish. Evidence from randomized controlled trials suggests potential efficacy of FMT in UC, particularly with intensive or repeated protocols, whereas data in CD remain limited and heterogeneous, with signals of benefit often appearing transient. FMT was generally well tolerated, but long-term safety data remain scarce. Emerging multi-omic approaches are reshaping the field by integrating taxonomic and functional insights, with potential implications for risk stratification, diagnosis, prognosis, and therapeutic optimization. Further standardized, longitudinal, and mechanistically oriented studies are required to translate microbiome research into clinically actionable strategies in IBD. Full article

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12 pages, 1706 KB

Open AccessArticle

Transferrin Receptor Marks a Foxp3-Low Treg-like Inflammatory T Cell Subset Associated with Disease Severity in HAM/TSP

by Shinsuke Nakajima, Masaki Hino, Norihiro Takenouchi, Yoshihisa Yamano, Makoto Yamagishi, Tokifumi Odaka, Fhahira Rizkhika Admadiani, Cecile Faye, Kaoru Uchimaru, Jun-Ichi Fujisawa and Kazu Okuma

Pathogens 2026, 15(4), 450; https://doi.org/10.3390/pathogens15040450 - 21 Apr 2026

Viewed by 620

Abstract

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease driven by HTLV-1-infected CD4⁺ T cells; however, the phenotypic and functional characteristics of disease-associated T-cell subsets remain incompletely understood. We analyzed samples using flow cytometry ( [...] Read more.

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease driven by HTLV-1-infected CD4⁺ T cells; however, the phenotypic and functional characteristics of disease-associated T-cell subsets remain incompletely understood. We analyzed samples using flow cytometry (n = 3–5 per group) and RNA-seq (n = 13), focusing on CADM1^highCD4⁺ T cells enriched for HTLV-1-infected cells to evaluate a transferrin receptor (TfR)-expressing subset. TfR⁺CADM1^highCD4⁺ T cells were detected in both asymptomatic carriers and patients with HAM, but their frequency among CD4⁺ T cells was higher in HAM patients. These cells exhibited a Treg-like phenotype with higher Foxp3 and CTLA-4 expression than TfR⁻ cells and showed increased Ki-67 positivity, consistent with proliferation. Despite this phenotype, they produced interferon-γ, indicating inflammatory potential, while Foxp3 expression was lower in HAM patients than in asymptomatic carriers, suggesting a more inflammatory phenotype. Furthermore, TfR transcript levels (RNA-seq TPM) correlated with clinical indicators of disease activity, including neopterin and CXCL10 protein levels, and the Osame motor disability score. Collectively, these findings suggest that TfR identifies a proliferative, Foxp3-low, Treg-like inflammatory CD4⁺ T-cell subset that is associated with disease activity in HAM. Full article

(This article belongs to the Special Issue New Insights into HTLV-1-Related Inflammatory Diseases)

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25 pages, 4282 KB

Open AccessReview

Sulbactam–Durlobactam for Carbapenem-Resistant Acinetobacter baumannii–calcoaceticus Complex

by Francesco Nappi

Pathogens 2026, 15(4), 449; https://doi.org/10.3390/pathogens15040449 - 21 Apr 2026

Viewed by 1499

Abstract

Carbapenem-resistant Acinetobacter baumannii infections pose a significant challenge due to their severity and the poor prognoses they often result in, particularly in cases where there are risk factors present. The United States (US) Centers for Disease Control and Prevention (CDC) identified carbapenem-resistant Acinetobacter [...] Read more.

Carbapenem-resistant Acinetobacter baumannii infections pose a significant challenge due to their severity and the poor prognoses they often result in, particularly in cases where there are risk factors present. The United States (US) Centers for Disease Control and Prevention (CDC) identified carbapenem-resistant Acinetobacter baumannii (CRAB) infections as a threat to human health. The World Health Organization (WHO) has classified it as a top priority for research. In 2023, the US FDA approved sulbactam–durlobactam for treating certain A. baumannii infections. As of 2024, this combination is designated as the preferred treatment strategy by the Infectious Diseases Society of America (IDSA) for infections due to carbapenem-resistant A. baumannii. In this therapeutic review, the preclinical and clinical data relevant to this regulatory decision were analyzed. This in-depth analysis will provide a comprehensive overview of the complex subject matter. It should be observed that carbapenem-based combination therapy is indicated for carbapenem-resistant A. baumannii. Full article

(This article belongs to the Section Bacterial Pathogens)

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14 pages, 11134 KB

Open AccessArticle

Efficient and Stable Subcellular Protein Labeling in Leishmania mexicana Using a Re-Engineered mNeonGreen Integration Vector

by Tianyu Lei, Mengtao Yu, Panjing Lv, Hui Deng, Di Yang, Kaijie Li and Yan Li

Pathogens 2026, 15(4), 448; https://doi.org/10.3390/pathogens15040448 - 21 Apr 2026

Viewed by 522

Abstract

The protozoan parasite Leishmania mexicana serves as a widely used model for studying trypanosomatid biology, yet the demand for stable, high-intensity fluorescent tools for precise subcellular protein localization remains unmet. In this study, we developed a versatile molecular toolbox by re-engineering the pLEXSY-hyg2.1 [...] Read more.

The protozoan parasite Leishmania mexicana serves as a widely used model for studying trypanosomatid biology, yet the demand for stable, high-intensity fluorescent tools for precise subcellular protein localization remains unmet. In this study, we developed a versatile molecular toolbox by re-engineering the pLEXSY-hyg2.1 vector to express mNeonGreen (mNG), a next-generation fluorophore with superior brightness and photostability. Using a modular cloning strategy, we introduced a customized multiple cloning site (MCS) upstream of the mNG sequence to facilitate seamless N-terminal tagging of target proteins. The construct was integrated into the 18S rRNA locus via homologous recombination to ensure stable, constitutive expression. As a proof-of-concept, we fused a flagellar marker to the mNG reporter, resulting in a transgenic line exhibiting robust and specific subcellular fluorescence without compromising cellular fitness. Our results demonstrate that this integration-based system provides a highly efficient and stable platform for visualizing protein distribution within Leishmania. This tool significantly simplifies the generation of reporter strains and will facilitate high-resolution imaging studies of parasite organelle dynamics and functional genomics. Full article

(This article belongs to the Special Issue Leishmaniasis in East Asia)

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1 pages, 145 KB

Open AccessCorrection

Correction: Pérez-Prieto et al. Are Hamstring Grafts a Predisposing Factor to Infection in R-ACL Surgery? A Comparative In Vitro Study. Pathogens 2023, 12, 761

by Daniel Pérez-Prieto, Svetlana Karbysheva, Andrej Trampuz, Oscar Fariñas, Joan C. Monllau and Ferran Corcoll

Pathogens 2026, 15(4), 447; https://doi.org/10.3390/pathogens15040447 - 21 Apr 2026

Viewed by 255

Abstract

In the original publication [...] Full article

(This article belongs to the Section Bacterial Pathogens)

14 pages, 1203 KB

Open AccessArticle

Global Patterns of Human Rhinovirus Activity and Epidemic Duration, 2016–2025: Before, During, and After the COVID-19 Pandemic

by Alessandra Picelli, Emma Papini, Guglielmo Bonaccorsi, Angela Bechini, Fabiola Berti, Sara Boccalini, Paolo Bonanni, Manuela Chiavarini, Claudia Cosma, Chiara Lorini, Cristina Salvati, Valentina Saviozzi, Patrizio Zanobini, Marco Del Riccio and Saverio Caini

Pathogens 2026, 15(4), 446; https://doi.org/10.3390/pathogens15040446 - 20 Apr 2026

Viewed by 885

Abstract

Background: Human rhinoviruses (HRVs) exhibit a global circulation characterized by prolonged epidemics and a less concentrated seasonal distribution compared with other respiratory viruses. In this study, we describe the timing, amplitude and duration of HRV epidemics on a global scale, analyzing seasonal patterns [...] Read more.

Background: Human rhinoviruses (HRVs) exhibit a global circulation characterized by prolonged epidemics and a less concentrated seasonal distribution compared with other respiratory viruses. In this study, we describe the timing, amplitude and duration of HRV epidemics on a global scale, analyzing seasonal patterns in relation to geographic latitude. Methods: HRV surveillance data reported to WHO FluNet from 2016 to 2025 were analyzed. Epidemic peak timing, amplitude and duration were estimated as a function of geographic latitude using harmonic analyses, with a comparison between the pre-pandemic (2016–2019) and post-pandemic (2021–2025) periods. Results: During the study period, 432,399 HRV detections were reported to WHO FluNet across 50 countries. Among these, 24 countries met the predefined criteria for seasonal analysis. Epidemic peak timing showed differences consistent with latitude, with peaks occurring in late autumn and winter in the Northern Hemisphere, during the central months of the year in the Southern Hemisphere, and greater temporal variability in the intertropical belt. Peak amplitude showed marked heterogeneity across countries (median 68.2%, range 28.1–96.7%), while epidemic duration indicated prolonged circulation (median 31 weeks, range 5–48 weeks). A secondary seasonal peak was identifiable in most countries, further supporting the relatively diffuse seasonal profile of HRV circulation. Comparison between the pre- and post-pandemic periods showed largely stable peak timing in most countries, alongside heterogeneous changes in peak amplitude. Conclusions: HRV is characterized by prolonged and weakly concentrated seasonal activity, with epidemic circulation often extending over several months. Despite major epidemiological perturbations during the COVID-19 pandemic, the timing of seasonal peaks remained largely stable across countries, highlighting the epidemiological resilience of HRV and the need for continuous, pathogen-specific surveillance. Full article

(This article belongs to the Section Viral Pathogens)

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10 pages, 2527 KB

Open AccessArticle

First Report of Kalmusia variispora Causing Bark Necrosis and Branch Dieback of Horse Chestnut (Aesculus hippocastanum L.)

by Miłosz Tkaczyk and Katarzyna Sikora

Pathogens 2026, 15(4), 445; https://doi.org/10.3390/pathogens15040445 - 20 Apr 2026

Cited by 1 | Viewed by 498

Abstract

Horse chestnut (Aesculus hippocastanum L.) is a widely planted ornamental and urban tree valued for its aesthetic and ecological functions. In recent years, declining health of horse chestnut in urban environments has been increasingly reported, often associated with a complex of biotic [...] Read more.

Horse chestnut (Aesculus hippocastanum L.) is a widely planted ornamental and urban tree valued for its aesthetic and ecological functions. In recent years, declining health of horse chestnut in urban environments has been increasingly reported, often associated with a complex of biotic and abiotic stressors. During a health survey of A. hippocastanum trees growing along an urban road corridor in Warsaw, Poland, extensive bark necrosis and branch dieback were observed. The aim of this study was to identify the causal agent of these symptoms using morphological, cultural, molecular (ITS rDNA), and pathogenicity tests under controlled conditions. Fungal isolates were obtained from necrotic tissues and were consistently identified as Kalmusia variispora based on ITS sequence analysis (99.0–99.6% similarity to GenBank references) and characteristic morphology. Pathogenicity tests fulfilled Koch’s postulates, reproducing necrotic lesions and cambial damage similar to those observed in the field. To our knowledge, this is the first documented report worldwide of K. variispora infecting A. hippocastanum. The findings expand the known host range of this opportunistic Didymosphaeriaceae species and highlight its potential role in bark and wood disease complexes of urban trees. Further research is needed to assess its distribution, genetic diversity, and epidemiological significance in urban forest ecosystems. Full article

(This article belongs to the Section Fungal Pathogens)

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21 pages, 1094 KB

Open AccessReview

Subverting Host Defense from Within: Innate Immune Modulation by Coxiella burnetii

by Anna O. Busbee, Aryashree Arunima, James E. Samuel and Erin J. van Schaik

Pathogens 2026, 15(4), 444; https://doi.org/10.3390/pathogens15040444 - 20 Apr 2026

Viewed by 1424

Abstract

C. burnetii (Cb) is an obligate intracellular bacterial pathogen that replicates within alveolar macrophages following aerosol infection. Unlike most intracellular bacteria, Cb establishes a lysosome-derived replicative niche (Coxiella-containing vacuole or CCV) through the action of its Type IVB secretion system (T4BSS). [...] Read more.

C. burnetii (Cb) is an obligate intracellular bacterial pathogen that replicates within alveolar macrophages following aerosol infection. Unlike most intracellular bacteria, Cb establishes a lysosome-derived replicative niche (Coxiella-containing vacuole or CCV) through the action of its Type IVB secretion system (T4BSS). This system translocates a large repertoire of effector proteins into the host cytoplasm after phagosome acidification. These effectors interfere with diverse signaling pathways to co-opt host processes, such as vesicle trafficking, ubiquitylation, gene expression and lipid metabolism, promoting pathogen survival without triggering robust proinflammatory signaling or host cell death pathways. This effector-triggered immune silencing is particularly unique given the central role of macrophages as innate immune sentinels. In this review, we examine Cb T4BSS effectors that have been characterized as central determinants of innate immunity modulation. We discuss innate immune sensing pathways potentially engaged during infection, including Toll-like receptors, NOD-like receptors, RIG-I-like receptors, inflammasomes, and interferon signaling pathways, and highlight evidence indicating that these pathways are actively suppressed. Emphasis is placed on effector-mediated regulation of NF-κB signaling, type I interferon responses, and inflammasome activation. Finally, we address unresolved questions related to effector-triggered immunity, redundancy in immune suppression, and discrepancies between in vitro and in vivo infection models. Full article

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

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28 pages, 1569 KB

Open AccessReview

Nipah Virus Encephalitis: Pathogenetic Aspects and Current Therapeutic Strategies

by Gaetano Scotto, Vincenzina Fazio, Ali Muhammed Moula, Sri Charan Bindu Bavisetty, Alessia Franza and Salvatore Massa

Pathogens 2026, 15(4), 443; https://doi.org/10.3390/pathogens15040443 - 20 Apr 2026

Viewed by 1342

Abstract

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus responsible for sporadic outbreaks of severe disease with high case fatality rates in South and Southeast Asia. Human infection occurs through spillover from natural reservoirs, primarily fruit bats, or via human-to-human transmission, and is [...] Read more.

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus responsible for sporadic outbreaks of severe disease with high case fatality rates in South and Southeast Asia. Human infection occurs through spillover from natural reservoirs, primarily fruit bats, or via human-to-human transmission, and is characterized by a broad clinical spectrum ranging from asymptomatic infection to acute respiratory disease and fatal encephalitis. Following entry via ephrin-B2 and ephrin-B3 receptors, NiV exhibits marked endothelial and neuronal tropism, leading to systemic vasculitis, disruption of the blood–brain barrier, and direct infection of the central nervous system. Disease progression is driven by a complex interplay between viral replication strategies and host immune responses. NiV effectively counteracts innate immunity through multiple viral proteins that inhibit interferon signaling, while simultaneously inducing dysregulated inflammatory responses that contribute to tissue damage and multi-organ failure. Neurological involvement represents the most severe manifestation, often resulting in acute or relapsing encephalitis with long-term sequelae among survivors. Despite the severity of the disease, no licensed antiviral therapies or human vaccines are currently available. Therapeutic development has focused on neutralizing monoclonal antibodies targeting viral glycoproteins and small-molecule antivirals that inhibit viral RNA synthesis, both of which show promising results in preclinical models, but remain limited by timing and translational challenges. In parallel, several vaccine platforms—including viral vectors, mRNA-based constructs, and recombinant protein subunits—have advanced to early-phase clinical trials, demonstrating encouraging immunogenicity. Beyond biomedical interventions, effective outbreak containment relies on integrated public health strategies. The “Kerala model” highlights the importance of rapid case identification, isolation, contact tracing, and community engagement within a One Health framework to mitigate transmission and reduce mortality. This review synthesizes the current knowledge on NiV pathogenesis, immune evasion, clinical manifestations, and emerging therapeutic and vaccine strategies, while highlighting critical gaps and future directions for improving the preparedness and response to this high-consequence emerging pathogen. Full article

(This article belongs to the Section Viral Pathogens)

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18 pages, 1192 KB

Open AccessReview

Pathogen Reduction of Transfused Blood Components—The End of the Beginning Rather than the Beginning of the End

by Albert Farrugia, Laurence Corash, Raymond Goodrich and Leni von Bonsdorff

Pathogens 2026, 15(4), 442; https://doi.org/10.3390/pathogens15040442 - 20 Apr 2026

Viewed by 975

Abstract

Therapeutics derived from donated blood or its constituents are classifiable into blood components and plasma derivatives. The latter are defined as medicines/drugs/pharmaceuticals produced from the industrial fractionation of thousands of pooled plasma donations and characterised with relative precision to a pre-defined specification through [...] Read more.

Therapeutics derived from donated blood or its constituents are classifiable into blood components and plasma derivatives. The latter are defined as medicines/drugs/pharmaceuticals produced from the industrial fractionation of thousands of pooled plasma donations and characterised with relative precision to a pre-defined specification through sampling of a homogenous pharmaceutical batch. The former are defined as components/biologicals produced using relatively simple (but increasingly complex) technologies in blood centres from single or small pools of isolated components from whole blood and are pre-specified through regulatory standards with relatively wide limits because of the inherent biologic variability of individual donors. This review discusses the evolution of technology to reduce the risk of pathogen transmission by blood-derived therapeutics, assess the state of the approved technologies for pathogen-reduced blood components, and examine the features of the blood-provider and regulatory framework globally that have shaped, and in some instances impeded, the implementation of component pathogen reduction to an extent equivalent to that achieved for plasma derivatives. The ensuing risks to the public’s confidence in the blood supply are discussed, and remedial actions are proposed. The features of a new paradigm for blood safety are outlined. Full article

(This article belongs to the Special Issue Globalisation of Pathogen Safety Threats to the Blood Supply)

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19 pages, 8753 KB

Open AccessArticle

Interferon-β Modulates Early Viral Replication Kinetics and Innate Responses to Non-Fatal Alphavirus Encephalomyelitis

by Benjamin H. Nguyen, Elise Stanley, Victoria K. Baxter and Diane E. Griffin

Pathogens 2026, 15(4), 441; https://doi.org/10.3390/pathogens15040441 - 18 Apr 2026

Viewed by 677

Abstract

Alphaviruses are mosquito-borne viruses that can infect the central nervous system (CNS) and cause encephalomyelitis, which is a rare but dangerous complication from infection. In mice, this can be studied in a model of infection with Sindbis virus (SINV), which infects neurons and [...] Read more.

Alphaviruses are mosquito-borne viruses that can infect the central nervous system (CNS) and cause encephalomyelitis, which is a rare but dangerous complication from infection. In mice, this can be studied in a model of infection with Sindbis virus (SINV), which infects neurons and causes neurological disease. Due to the non-renewable nature of neurons, the immune response in the CNS is specialized to prevent neuronal damage or death, even if they are infected. Therefore, insights into the nuances of antiviral immunity in the CNS provide a better understanding of disease pathogenesis and mechanisms of recovery. Type I interferons (IFNs) are critically important for survival; they are an innate antiviral defense mechanism that consists mainly of IFNα and IFNβ. Although both use the same receptor, type-specific differences between IFNα and IFNβ have been described in other contexts. To this end, Ifnb^−/− mice were used to elucidate the role of IFNβ in recovery from alphavirus encephalomyelitis. IFNβ-deficient mice have intact IFNα expression and downstream signaling, but symptomatic disease occurs earlier and is more severe. This is accompanied by increased virus replication in the early stages of infection. Microgliosis is reduced in Ifnb^−/− mice compared to wildtype, but inflammatory cytokine/chemokine levels are higher and associated with alterations in monocyte and NK cell recruitment into the CNS. Ifnb^−/− mice have no deficiencies in the expression of factors known to be required for viral clearance. Therefore, IFNβ modulates the early stages of the immune response and facilitates restriction of virus replication, contributing to delayed disease onset. Full article

(This article belongs to the Special Issue Arboviruses Infections and Pathogenesis)

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20 pages, 1160 KB

Open AccessReview

Ecological Frameworks of Pathogen–Pathogen and Pathogen–Microbiome Interactions Within the Tick Holobiont

by Elianne Piloto-Sardiñas, Islay Rodríguez, Huarrisson Azevedo Santos, Patrícia Gonzaga Paulino, Belkis Corona-González and Alejandro Cabezas-Cruz

Pathogens 2026, 15(4), 440; https://doi.org/10.3390/pathogens15040440 - 18 Apr 2026

Cited by 1 | Viewed by 728

Abstract

Ticks harbor complex microbial communities composed of symbionts, commensals, and tick-borne pathogens (TBPs). Together, these microorganisms form the tick holobiont. Within this system, the tick’s physiological architecture structures microbial communities by distributing microorganisms across distinct tissues. This compartmentalization creates spatially distinct ecological niches, [...] Read more.

Ticks harbor complex microbial communities composed of symbionts, commensals, and tick-borne pathogens (TBPs). Together, these microorganisms form the tick holobiont. Within this system, the tick’s physiological architecture structures microbial communities by distributing microorganisms across distinct tissues. This compartmentalization creates spatially distinct ecological niches, which in turn shape how microbial communities assemble and interact. In this review, we integrate ecological theory with current knowledge of tick microbiome research to examine how pathogen–pathogen and pathogen–microbiome interactions emerge within these tissue-structured microbial communities. We first outline how baseline ecological filters, including tick species, developmental stage, tissue identity, vertical transmission, and environmental context, shape the microbiome configuration through community assembly processes. We then examined how TBPs, as high-impact colonizers, can further modify microbial networks by altering host-mediated selective pressures, influencing interaction topology, and reshaping community stability. Based on these observations, we propose a dual selective pressure framework in which (i) baseline ecological structuring processes and (ii) pathogen-associated selective pressures interact to determine the microbial network configuration and functional outcomes within the tick holobiont. These interacting forces may drive shifts in diversity, modularity, keystone taxa emergence, and network resilience, ultimately influencing vector competence. This review frames the microbial communities within the tick holobiont as spatially structured ecological systems shaped by multilevel selective pressures. This conceptual foundation provides a coherent framework for understanding microbial interactions in arthropod vectors and highlights avenues for mechanistic research and microbiome-based strategies to mitigate tick-borne diseases. Full article

(This article belongs to the Special Issue Microbial Interactions in Ticks: Pathogen–Pathogen and Pathogen–Non-Pathogenic Microorganism Dynamics in Coinfections)

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13 pages, 2935 KB

Open AccessArticle

Pilot Assessment of RNA Stabilization Methods for Influenza A Virus in Swine Oral Fluids

by Berenice Munguía-Ramírez, Betsy Armenta-Leyva, Luis Giménez-Lirola, Yanqi Zhang, Bailey Arruda, Giovana Ciacci-Zanella and Jeffrey Zimmerman

Pathogens 2026, 15(4), 439; https://doi.org/10.3390/pathogens15040439 - 18 Apr 2026

Viewed by 810

Abstract

Influenza A virus (IAV) surveillance in swine relies heavily on molecular detection, yet RNA stability in diagnostic specimens such as oral fluids can be rapidly compromised when cold-chain conditions are not maintained. This pilot study evaluated the ability of four molecular-grade carbohydrates (20% [...] Read more.

Influenza A virus (IAV) surveillance in swine relies heavily on molecular detection, yet RNA stability in diagnostic specimens such as oral fluids can be rapidly compromised when cold-chain conditions are not maintained. This pilot study evaluated the ability of four molecular-grade carbohydrates (20% trehalose, sorbitol, sucrose, and mannitol) and two commercial nucleic acid stabilizers (PrimeStore^® MTM and RNAlater^®) to preserve RT-qPCR-detectable IAV RNA in swine oral fluids exposed to field-relevant stress conditions. Oral fluid samples collected from pigs experimentally infected with H1N2 (Study 1: n = 150; DPIs 2, 3, 4) or with H1N2 and H3N2 (Study 2: n = 58; DPI 5) were subjected to storage at 25 °C for up to 144 h (Study 1) or 2, 5, 10, or 15 freeze–thaw cycles (Study 2), with DPIs (Study 1) or subtypes (Study 2) serving as biological replicates, given the limited sample size. IAV detection was quantified as efficiency standardized Cq values (ECq) and analyzed using a linear mixed-effects model. Overall, both carbohydrates (trehalose, sorbitol, sucrose) and commercial stabilizers maintained higher ECq values than untreated oral fluids under both thermal and freeze–thaw stress conditions. Due to the limited sample size, these findings should be interpreted cautiously, yet they demonstrate the potential utility of carbohydrates as a low-cost, non-inactivating alternative for stabilizing IAV RNA in field-collected oral fluids. Full article

(This article belongs to the Section Viral Pathogens)

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18 pages, 1320 KB

Open AccessArticle

Genomic Diversity and Virulence Potential of High-Priority Critically Important Antimicrobial-Resistant Escherichia coli from Pork and Chicken Retail Meat

by Hernán D. Nievas, Camila Aurnague, Elisa Helman, Raúl E. Iza, Magdalena Costa, Oliver Mounsey, Matthew B. Avison, Lucía Galli and Fabiana A. Moredo

Pathogens 2026, 15(4), 438; https://doi.org/10.3390/pathogens15040438 - 18 Apr 2026

Viewed by 731

Abstract

The occurrence of Escherichia coli resistant to high-priority critically important antimicrobials (HPCIA) in the food chain is a growing concern for food safety and public health. This study aimed to evaluate whether HPCIA-resistant E. coli isolated from pork and chicken meat at retail [...] Read more.

The occurrence of Escherichia coli resistant to high-priority critically important antimicrobials (HPCIA) in the food chain is a growing concern for food safety and public health. This study aimed to evaluate whether HPCIA-resistant E. coli isolated from pork and chicken meat at retail markets in La Plata, Buenos Aires, Argentina, exhibit source-associated genomic differentiation through whole-genome sequencing. The isolates displayed a polyclonal population structure, encompassing multiple phylogenetic groups and sequence types. Virulence gene profiles were highly diverse, with chicken-derived isolates harbouring a substantially higher number of virulence genes than pork isolates. Notably, one pork isolate carried a complete set of virulence genes characteristic of diarrheagenic E. coli. Single Nucleotide Polymorphism-based phylogenetic analysis revealed several closely related subclusters, including strains recovered from both pork and chicken meat from the same retail markets, suggesting recent clonal sharing or cross-contamination at the point of sale. These findings highlight the circulation of genetically diverse HPCIA-resistant E. coli in retail meat, underscoring the potential public health risk and the importance of monitoring resistance and virulence determinants throughout the food production chain. Full article

(This article belongs to the Special Issue Next-Gen Sequencing Advances Pathogen Research in Health, Agriculture & Environment)

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7 pages, 393 KB

Open AccessCase Report

Imported Pediatric Lyme Disease in Singapore—A Case Series

by Ade Xin Ning Tan, Ilyas Hussin, Chia Yin Chong, Matthias Maiwald, Terri Xiao-Bei Chiong and Natalie Woon Hui Tan

Pathogens 2026, 15(4), 437; https://doi.org/10.3390/pathogens15040437 - 17 Apr 2026

Viewed by 656

Abstract

Lyme disease is the most common reported vector-borne disease in North America and is also highly prevalent across Europe. Although tick-borne diseases are uncommon in Singapore, there remains a risk of imported tick-borne diseases among travelers from endemic regions. We present a case [...] Read more.

Lyme disease is the most common reported vector-borne disease in North America and is also highly prevalent across Europe. Although tick-borne diseases are uncommon in Singapore, there remains a risk of imported tick-borne diseases among travelers from endemic regions. We present a case series of three pediatric patients with imported Lyme disease managed at a tertiary children’s hospital in Singapore, illustrating the varied clinical presentations of Lyme disease in children. One child developed meningitis following prior antibiotic therapy for Lyme disease, although causality cannot be definitively established. This series aims to highlight key diagnostic considerations and management principles relevant to clinicians practicing in non-endemic regions. Full article

(This article belongs to the Special Issue Ticks and Tick-Borne Diseases in Southeast Asia)

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10 pages, 2492 KB

Open AccessArticle

In Murine Disseminated Candidiasis, Serum Amyloid P Component Inhibits Inflammation and C-Reactive Protein Potentiates Inflammation

by Stephen A. Klotz, Richard E. Sobonya and Peter N. Lipke

Pathogens 2026, 15(4), 436; https://doi.org/10.3390/pathogens15040436 - 17 Apr 2026

Viewed by 412

Abstract

Candida albicans is a ubiquitous commensal fungus that may be lethal once it gains access to the bloodstream, following a breach in protective barriers such as skin or gut lining. Intravenous injection of C. albicans (4.5 × 10⁴ yeasts/gm of mouse) leads [...] Read more.

Candida albicans is a ubiquitous commensal fungus that may be lethal once it gains access to the bloodstream, following a breach in protective barriers such as skin or gut lining. Intravenous injection of C. albicans (4.5 × 10⁴ yeasts/gm of mouse) leads reproducibly to systemic infection with a median survival of about 75 h. We studied the effects of two human innate immune effectors on the course of systemic infections. The soluble human pentraxin serum amyloid P component (hSAP) retards death in murine disseminated candidiasis. In contrast, another soluble pentraxin, human C-reactive protein (hCRP), hastens death. To examine the pathological basis for these differences, necropsies were performed, and the right kidney was removed for study. Candidiasis caused abundant collagen deposition (the precursor to fibrosis) and loss of contrast between the kidney medulla and cortex. Daily administration of subcutaneous hSAP following the intravenous injection of C. albicans preserved the discrete histological difference between cortex and medulla and lessened host collagen deposition. Yeasts and hyphae within abscesses were decorated with hSAP. Contrastingly, kidneys from animals administered C. albicans and hCRP showed extensive collagen deposition and loss of the boundary between the cortex and the medulla of the kidney. hCRP did not bind to fungi but bound to damaged tissue surrounding abscesses, leading to a more destructive infection with loss of tissue. Staining cells with antibodies to CD45 (to detect T-lymphocytes, myelocytes, monocytes, and macrophages) and antibodies to Ly-6G (neutrophils, and granulocytes) showed that hSAP retarded infiltration of inflammatory cells into diseased areas. The results are consistent with the hypothesis that early administration of hSAP represses the migration of inflammatory cells, dampens the production of collagen by fibroblasts, and dampens the overall immune response of the host to infection. In doing so, hSAP prolonged life, whereas hCRP facilitated the infectious process and hastened death. Full article

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

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12 pages, 1006 KB

Open AccessArticle

Molecular Characterization and Preliminary NGS Profiling of Terbinafine-Resistant Trichophyton indotineae Isolates in Italy

by Deborah Cruciani, Manuela Papini, Luigi Pisano, Roberta Calcaterra, Donatella Pietrella, Tommaso Galeotti, Paolo Fazii, Antonia Meloscia, Martina Torricelli, Marco Di Domenico, Alessandro Fiorucci, Sara Spina and Silvia Crotti

Pathogens 2026, 15(4), 435; https://doi.org/10.3390/pathogens15040435 - 17 Apr 2026

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Abstract

Trichophyton indotineae is an emerging dermatophyte associated with extensive, chronic, recalcitrant, and frequently terbinafine-resistant dermatophytosis worldwide. In this study, 30 T. indotineae strains isolated in Italy were investigated. The isolates were obtained from patients originating from Asian countries, from patients from other countries, [...] Read more.

Trichophyton indotineae is an emerging dermatophyte associated with extensive, chronic, recalcitrant, and frequently terbinafine-resistant dermatophytosis worldwide. In this study, 30 T. indotineae strains isolated in Italy were investigated. The isolates were obtained from patients originating from Asian countries, from patients from other countries, and from Italian patients who reported no travel outside Italy in the preceding years. Clinical isolates were identified by internal transcribed spacer (ITS) sequencing and analyzed to assess the occurrence and molecular basis of terbinafine resistance. Terbinafine resistance was detected in 18 strains (60%) using a real-time PCR assay. Sequencing of the squalene epoxidase (SQLE) gene revealed mutations associated with resistance, including L393S in nine strains and F397L in another nine strains. NGS analysis confirmed two terbinafine-resistant strains carrying the L393S and F397L mutations, respectively, and detected the A448T mutation in one terbinafine-susceptible strain. These findings demonstrate the presence of terbinafine-resistant T. indotineae across five regions of Italy and confirm the occurrence of SQLE mutations previously linked to antifungal resistance. Data obtained also support a link with endemic Asian areas, other than suggesting the possible occurrence of autochthonous transmission in Italy. Full article

(This article belongs to the Special Issue Epidemiology and Molecular Detection of Emerging Fungal Pathogens)

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14 pages, 826 KB

Open AccessArticle

Assessment of IL-6 and IL-8 Levels and Other Bio Markers in Predicting Dengue Severity Across Serotypes

by Kumar Sivasubramanian, Rudrappan Raj Bharath, Leela Kakithakara Vajravelu, Madan Kumar D and Jayakrishna Pamarthi

Pathogens 2026, 15(4), 434; https://doi.org/10.3390/pathogens15040434 - 17 Apr 2026

Viewed by 908

Abstract

Background: Dengue fever is one of the most common mosquito-borne viral infections, with severe cases characterized by plasma leakage, hemorrhage, and multi-organ involvement. Identification of dengue serotypes and reliable biomarkers is essential for predicting disease progression and guiding timely interventions. Methods: This prospective [...] Read more.

Background: Dengue fever is one of the most common mosquito-borne viral infections, with severe cases characterized by plasma leakage, hemorrhage, and multi-organ involvement. Identification of dengue serotypes and reliable biomarkers is essential for predicting disease progression and guiding timely interventions. Methods: This prospective cohort study was conducted at a super-speciality tertiary care hospital in southern India from July 2024 to July 2025. A total of 69 patients presenting with dengue warning signs were included in the study. Patients were categorized into the severe dengue group (n = 25) and non severe dengue group (n = 44). Clinical data, laboratory findings, dengue serotype, and serial serum samples collected on Days 1, 4, and 8 were analyzed to evaluate the predictive and monitoring efficacy of Interleukin-6 (IL-6) and Interleukin-8 (IL-8), and followed up till discharge. Results: Out of 69 dengue patients with warning signs, 32 dengue-positive patients were serotyped, which included DEN V-1 (31.3%), DEN V-2 (31.3%), DEN V-3 (15.6%), DEN V-4 (18.8%), and mixed DEN V-(2 + 3) (3.1%). Severe dengue patients exhibited a higher frequency of secondary dengue infection (IgG) than primary dengue infection (88% vs. 12%), with statistically significantly higher packed cell volume, hemoglobin levels, high AST levels, and prolonged activated partial thromboplastin time, as well as lower platelet counts and albumin levels. Platelet transfusion was given to 35 dengue patients, which had also resulted in significant length of stay in hospital in comparison to non-transfused patients. IL-6 and IL-8 levels were significantly elevated in severe dengue patients when compared to non-severe dengue patients on Day 1 and Day 4, followed by a decline on Day 8, corresponding with clinical recovery. However, the elevated IL-8 levels were observed to be significantly associated with longer hospital stays, indicating its potential role as an early predictor of disease progression. Conclusions: The observed co-circulation of multiple serotypes reflects the hyper-endemic pattern reported across India. Early measurement of these cytokines IL-6 and IL-8 helps distinguish severe from non-severe dengue among patients presenting with warning signs. IL-6 and IL-8 may have potential as biomarkers for disease severity. However their role in guiding platelet transfusion requires further investigation in non-severe cases and prioritizing timely management for those at higher risk of severe disease. Full article

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

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15 pages, 1007 KB

Open AccessArticle

Impact of Vitamin D3 Supplementation on 28-Day ICU Mortality in Sepsis Patients: A Retrospective Study with Propensity Score Matching

by Xiaofei Huang, Anqiang Zhang, Dalin Wen, He Li and Ling Zeng

Pathogens 2026, 15(4), 433; https://doi.org/10.3390/pathogens15040433 - 16 Apr 2026

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Abstract

Reduced levels of vitamin D are associated with increased incidence and mortality of sepsis. Nonetheless, the effectiveness of vitamin D supplementation in improving sepsis patients’ outcomes continues to be debated. In this research, which was conducted as a retrospective cohort analysis, data obtained [...] Read more.

Reduced levels of vitamin D are associated with increased incidence and mortality of sepsis. Nonetheless, the effectiveness of vitamin D supplementation in improving sepsis patients’ outcomes continues to be debated. In this research, which was conducted as a retrospective cohort analysis, data obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV 3.0) were used. The focus of the study was on vitamin D3 administration to sepsis patients while in the ICU. The primary outcome measurement was 28-day ICU mortality, with secondary outcomes of mechanical ventilation duration, percentage of patients receiving mechanical ventilation, and ICU stay length. The Kaplan–Meier curve analysis, Cox regression analysis, and subgroup analyses were performed to explore the link between vitamin D3 supplementation and sepsis prognosis. A 1:1 propensity score matching (PSM) approach was used to strengthen the reliability of the results. Before matching, the cohort comprised 28,524 patients, which was reduced to 4,856 after PSM. The analysis revealed that vitamin D3 supplementation was associated with a lower 28-day ICU mortality rate (HR = 0.71, 95% CI: 0.64–0.78, p < 0.001). Kaplan–Meier curve analysis revealed significantly greater survival probabilities in the group receiving vitamin D3 than in the group not receiving vitamin D3 (p < 0.001). Subgroup analysis showed that total cumulative exposure to vitamin D3 was more strongly associated with 28-day ICU mortality (p < 0.001), whereas daily dose and dosing frequency showed no significant association. The results after PSM and subgroup analysis were consistent with those of the original cohort study, further confirming the robustness of the results. Overall, vitamin D3 supplementation is associated with lower 28-day ICU mortality and better outcomes in patients with sepsis. However, given the retrospective observational design, large-scale prospective randomized controlled trials are warranted to validate these observational associations and establish causal effects. Full article

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15 pages, 2676 KB

Open AccessArticle

Functional and Biochemical Characterization of Spermidine Synthase CauSpe3 from Candidozyma auris

by Jae-Yeon Choi, Pallavi Singh and Choukri Ben Mamoun

Pathogens 2026, 15(4), 432; https://doi.org/10.3390/pathogens15040432 - 16 Apr 2026

Viewed by 513

Abstract

Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl [...] Read more.

Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl group from decarboxylated S-adenosylmethionine (dc-SAM) to putrescine to form spermidine. Although genomic analyses predict the presence of SPDS homologs in multiple fungal species, polyamine biosynthesis has not been experimentally characterized in the multidrug-resistant fungal pathogen Candidozyma auris. Here, we report the biochemical and functional characterization of the C. auris spermidine synthase, CauSpe3. The CauSPE3 gene complemented a Saccharomyces cerevisiae spe3Δ mutant demonstrating conserved function in vivo. Recombinant CauSpe3 was expressed in Escherichia coli, purified and analyzed using the fluorescence-based DAB-APT assay, which uses 1,2-diacetylbenzene (DAB) for polyamine detection. CauSpe3 catalyzed efficient conversion of putrescine to spermidine in the presence of dc-SAM, with K_half values of 65.5 ± 7.11 µM for putrescine and 66.9 ± 2.09 µM for dc-SAM, and V_max values of 7.1 ± 0.57 and 7.9 ± 0.12 nmol·µg⁻¹·min⁻¹, respectively. A catalytic-site mutant and heat-inactivated enzyme showed no detectable activity, and product formation was confirmed by means of thin-layer chromatography and mass spectrometry. These findings establish CauSpe3 as a functional spermidine synthase. Full article

(This article belongs to the Special Issue Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics)

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16 pages, 2755 KB

Open AccessArticle

HBV-Induced Pyruvate Increases Lactylation of Pyruvate Kinase M2 (PKM2) at K206 to Promote Liver Fibrosis

by Wenxian Wen, Qin Du, Shuhan Li, Youmin Yang, Xianding Wang, Shasha Li, Yujia Li, Shilin Li, Chunhui Yang, He Xie, Xiaoqiong Duan and Limin Chen

Pathogens 2026, 15(4), 431; https://doi.org/10.3390/pathogens15040431 - 16 Apr 2026

Viewed by 820

Abstract

We previously demonstrated that HBV promotes liver fibrosis through the enhanced production of pyruvate. Pyruvate kinase M2 (PKM2), a key enzyme in pyruvate metabolism, plays an important role in liver fibrogenesis. Recently, lactylation of PKM2 has been identified, which contributes to stabilize its [...] Read more.

We previously demonstrated that HBV promotes liver fibrosis through the enhanced production of pyruvate. Pyruvate kinase M2 (PKM2), a key enzyme in pyruvate metabolism, plays an important role in liver fibrogenesis. Recently, lactylation of PKM2 has been identified, which contributes to stabilize its catalytically active tetrameric conformation. Therefore, we hypothesize that PKM2 lactylation is involved in the regulation of HBV-induced liver fibrosis. In this study, we found that sera lactate levels were increased in CHB patients and HBV-Tg mice. Moreover, the lysine lactylation levels of proteins in liver tissues were significantly increased in the HBV-Tg mice. In LX2 cells, we found that pyruvate treatment significantly increased the profibrotic gene expression and lactylation level of PKM2, which promoted its tetramer-to-dimer transition, inhibited its pyruvate kinase activity, and facilitated its nuclear distribution. Through immunoprecipitation, we identified that pyruvate induced PKM2 lactylation at the K206 site. PKM2 knockdown or K206 mutation reduced PKM2 lactylation and abrogated the induction of profibrotic gene expression by pyruvate. Collectively, our findings indicate that HBV infection stimulated pyruvate production, which increased PKM2 lactylation at K206 to promote the expression of profibrogenic genes in HSCs, leading to liver fibrogenesis. Full article

(This article belongs to the Special Issue Viral Infections, Chronic Inflammation and Carcinogenesis)

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16 pages, 3492 KB

Open AccessArticle

Wild Boars as a Reservoir of Zoonotic Hepatitis E Virus in Portugal with Full-Genome Evidence of Genotype 3m

by Bernardo Almeida, Inês Caetano, Margarida Santos, Ana Duarte, Margarida Dias Duarte, Sílvia Carla Barros, Fábio A. Abade dos Santos and Ana Margarida Henriques

Pathogens 2026, 15(4), 430; https://doi.org/10.3390/pathogens15040430 - 16 Apr 2026

Viewed by 579

Abstract

Hepatitis E virus (HEV) is a zoonotic pathogen of global concern that circulates in both domestic and wild swine populations. Understanding its presence and dynamics in wildlife reservoirs is crucial for assessing spillover risks and designing One Health surveillance strategies. This study investigated [...] Read more.

Hepatitis E virus (HEV) is a zoonotic pathogen of global concern that circulates in both domestic and wild swine populations. Understanding its presence and dynamics in wildlife reservoirs is crucial for assessing spillover risks and designing One Health surveillance strategies. This study investigated the occurrence, genetic diversity, and evolutionary relationships of HEV in wild boars from mainland Portugal. A total of 120 animals from seven districts were tested, with HEV RNA detected in four cases (3.3%), all from the Évora district near the Spanish border. One positive sample was successfully sequenced, and phylogenetic analysis based on the complete genome classified it within the HEV-3m subtype, clustering with predominantly human-derived sequences from Spain and France, which highlights its zoonotic potential. A second phylogenetic analysis based on a partial genomic fragment, including sequences from domestic pigs in Portugal, revealed the co-circulation of subtypes 3e, 3f, and 3m without clear spatial or temporal patterns. Phylogeographic analysis suggested that the identified strain was most likely introduced from Spain, supporting the hypothesis of cross-border transmission through wild boar movement. No recombination events were detected in the sequence obtained in this study. These findings provide the first molecular evidence of HEV-3m circulation in wild boars in Portugal, offering valuable insight into the HEV strain circulation in European wildlife populations. The zoonotic potential of HEV and the likelihood of interspecies transmission highlight the need for coordinated cross-border surveillance and integrated One Health strategies. Full article

(This article belongs to the Section Viral Pathogens)

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18 pages, 4412 KB

Open AccessArticle

Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn’s Disease

by Carolina Hurtado-Marcos, Fernando Izquierdo, Soledad Fenoy, Carmen del Águila, Jaume Pérez-Griera, Salvador Benlloch, Cirilo Amorós, Carlos García Ballesteros, Francisca López Chuliá, Juan Carlos Andreu-Ballester and Carmen Cuéllar

Pathogens 2026, 15(4), 429; https://doi.org/10.3390/pathogens15040429 - 16 Apr 2026

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Abstract

Crohn’s disease (CD) is frequently accompanied by T-cell lymphopenia and impaired mucosal immunity, conditions that may predispose to intestinal microsporidiosis by Encephalitozoon cuniculi. This prospective case–control study examined the interplay between IL-7/IL-7 receptor (IL-7R) signaling and anti-E. cuniculi immune responses in [...] Read more.

Crohn’s disease (CD) is frequently accompanied by T-cell lymphopenia and impaired mucosal immunity, conditions that may predispose to intestinal microsporidiosis by Encephalitozoon cuniculi. This prospective case–control study examined the interplay between IL-7/IL-7 receptor (IL-7R) signaling and anti-E. cuniculi immune responses in 50 CD patients and 50 matched healthy controls. Serum IL-7 and anti-E. cuniculi IgG, IgM, IgA and IgE were quantified by ELISA, while intestinal expression of IL-7, CD127 (IL-7Rα) and CD132 (IL-7Rγ) was assessed by RT-PCR. Protein levels of IL-7 and caspase-3 were evaluated by Western blot, and lymphocyte subsets and apoptosis by flow cytometry. CD patients showed reduced anti-E. cuniculi IgG and IgM levels but increased seropositivity, indicating compromised humoral quality despite greater exposure. Compared with controls, CD was associated with decreased serum IL-7, increased mucosal IL-7, downregulated CD132, and diminished caspase-3, suggesting a disrupted IL-7/IL-7R-apoptosis pathway. In CD, IgA- and IgE-skewed responses correlated differentially with caspase-3 and CD56⁺ γδ T cells, while E. cuniculi seropositivity independently predicted a shorter surgery-free interval. These findings identify a profound dysregulation of the IL-7/IL-7R-CD132-caspase-3 axis in CD and implicate E. cuniculi exposure as a potential marker of impaired mucosal immunity and adverse outcomes. Full article

(This article belongs to the Section Parasitic Pathogens)

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19 pages, 4171 KB

Open AccessArticle

Occurrence and Genetic Diversity of Trichomonas gallinae in Captive Synanthropic Birds in Southeastern Brazil

by Amanda Garcia Pereira, Sarah Raquel Jesus Santos Simões, Maitê Cardoso Coelho da Silva, Ana Cláudia Calchi, Ricardo Bassini-Silva, Ana Carolina Castro-Santiago, Rosangela Zacarias Machado, Marcos Rogério André and Karin Werther

Pathogens 2026, 15(4), 428; https://doi.org/10.3390/pathogens15040428 - 16 Apr 2026

Viewed by 570

Abstract

Avian trichomonosis is caused by protozoa of the genus Trichomonas, mainly Trichomonas gallinae, which infects the upper digestive tract of birds and is commonly associated with Columbiformes, the main reservoirs of the parasite. This study aimed to investigate the occurrence and [...] Read more.

Avian trichomonosis is caused by protozoa of the genus Trichomonas, mainly Trichomonas gallinae, which infects the upper digestive tract of birds and is commonly associated with Columbiformes, the main reservoirs of the parasite. This study aimed to investigate the occurrence and genetic diversity of Trichomonas spp. in captive synanthropic birds from southeastern Brazil. Oropharyngeal swabs were collected from 281 birds belonging to 13 avian orders and analyzed using Diamond medium culture, Giemsa-stained smears, and molecular assays. Of the 262 samples submitted to culture analysis, 72 (27.48%) showed trophozoite-like structures under light microscopy. Molecular screening based on the ITS1–5.8S–ITS2 region detected Trichomonas DNA in 76 out of 267 samples with successful DNA extraction (28.46%), including 72 Columba livia domestica from Franca, one Coragyps atratus from Ribeirão Preto, and three rock doves from Jaboticabal. Among the ITS-positive samples, 67 (88.15%) amplified the Fe-hydrogenase gene, and 65 (85.5%) were also positive for the 18S rRNA gene. Only six samples (2.29%) exhibited structures compatible with Trichomonas spp. in Giemsa-stained smears. Phylogenetic analyses based on ITS sequences grouped the isolates into two clades within the Trichomonas gallinae complex. Greater genetic diversity was observed using Fe-hydrogenase and 18S rRNA markers, revealing multiple haplotypes and clades. Molecular assays, particularly PCR applied directly to oropharyngeal swabs, showed higher sensitivity for detecting and characterizing Trichomonas gallinae compared to culture and cytology. These findings highlight the high occurrence and genetic diversity of T. gallinae in captive synanthropic pigeons and reinforce the importance of molecular tools for epidemiological surveillance in wildlife facilities. Full article

(This article belongs to the Special Issue Biology, Epidemiology and Interactions of Parasitic Diseases)

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17 pages, 8679 KB

Open AccessArticle

The Interaction Between Echinococcus multilocularis Calreticulin S-Domain and Human Complement C1q Inhibits C1q-Dependent Immune Functions

by Meng Xia, Yinghui Song, Xiaofang Dong, Li Gu, Yishuo Wang, Wen Sun, Bin Zhan, Yan Yan and Limei Zhao

Pathogens 2026, 15(4), 427; https://doi.org/10.3390/pathogens15040427 - 16 Apr 2026

Cited by 1 | Viewed by 525

Abstract

EmCRT is a calreticulin secreted by Echinococcus multilocularis during its infection in host, playing an important role in evading host immune attack as a survival strategy. Our previous study has demonstrated that recombinant EmCRT (rEmCRT) was able to bind [...] Read more.

EmCRT is a calreticulin secreted by Echinococcus multilocularis during its infection in host, playing an important role in evading host immune attack as a survival strategy. Our previous study has demonstrated that recombinant EmCRT (rEmCRT) was able to bind to C1q and lectin to interfere with host classical and lectin complement activation pathway, respectively. However, the C1q-binding site on EmCRT and the associated immune evasion mechanism remain unknown. In this study, the C1q-binding site on EmCRT was determined through molecular docking analysis and fragment expression to be localized to the S-domain (EmCRT-S) between Lys¹⁴⁰ at the N-domain and Gln²⁹² at the P-domain. The recombinant EmCRT-S protein (rEmCRT-S) was subsequently expressed in bacteria. Functional analysis confirmed that rEmCRT-S was able to bind to human C1q and inhibit C1q-initiated complement activation at the similar level to the full-length rEmCRT, resulting in the reduction in C4b/C3b deposition and antibody-sensitized sheep red blood cell hemolysis. Furthermore, rEmCRT-S binding to C1q suppressed THP-1-derived macrophage chemotaxis and ROS generation. Given that the identified functional domain EmCRT-S provides similar complement regulatory functions to the full-length EmCRT, this domain is a more feasible and practical target for vaccine development against E. multilocularis infection or for inflammatory and autoimmune diseases. Full article

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

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10 pages, 1385 KB

Open AccessArticle

Multivariate Assessment of Microbiological and Incubation Data from an Experimental Trial Evaluating Essential Oil–Based Sanitizers and Formaldehyde on Hatching Eggs

by Vinícius Machado dos Santos, Gabriel da Silva Oliveira and Concepta McManus

Pathogens 2026, 15(4), 426; https://doi.org/10.3390/pathogens15040426 - 15 Apr 2026

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Abstract

Sanitization of hatching eggs is part of established poultry management practices, and its effectiveness is essential for productive success. This study aimed to investigate the relationships between microbiological and incubation performance variables obtained from a controlled experimental dataset of hatching eggs subjected to [...] Read more.

Sanitization of hatching eggs is part of established poultry management practices, and its effectiveness is essential for productive success. This study aimed to investigate the relationships between microbiological and incubation performance variables obtained from a controlled experimental dataset of hatching eggs subjected to sanitization with essential oils or not under commercial conditions, and to determine the efficacy of these sanitizers, using a multivariate approach. Data were analyzed using principal component, canonical, cluster, and discriminant analysis. The results suggested that bacterial contamination of the eggshell may promote internal contamination, leading to embryonic mortality. Essential oil-based treatments are associated with lower microbial indicators and improved hatchability, while formaldehyde showed an opposite trend despite its antibacterial efficacy. Multivariate analyses clarified the interrelationships between microbiological and incubation performance variables, allowing the identification of response patterns that evidenced the functional efficiency of essential oil–based treatments for hatching egg sanitization under commercial conditions. Full article

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18 pages, 1013 KB

Open AccessReview

Climate Change Impacts on Plant-Parasitic Nematodes in Agroecosystems

by Refik Bozbuğa, Furkan Ulaş, Özlem Urtekin, Muhammad Aasim, Mustafa İmren, Rachid Lahlali, Muhammad Amjad Ali, Fouad Mokrini and Abdelfattah Dababat

Pathogens 2026, 15(4), 425; https://doi.org/10.3390/pathogens15040425 - 14 Apr 2026

Viewed by 1116

Abstract

Climate change significantly impacts agricultural ecosystems through rising temperatures, changing precipitation patterns, increasing atmospheric CO₂ levels, and more frequent extreme weather events. These environmental changes have a pronounced effect on plant-parasitic nematodes (PPNs; phylum Nematoda), which cause serious crop losses on a [...] Read more.

Climate change significantly impacts agricultural ecosystems through rising temperatures, changing precipitation patterns, increasing atmospheric CO₂ levels, and more frequent extreme weather events. These environmental changes have a pronounced effect on plant-parasitic nematodes (PPNs; phylum Nematoda), which cause serious crop losses on a global scale. This review aims to provide a comprehensive evaluation of current knowledge on how major climate change drivers influence the biology, population dynamics, host–plant interactions, and geographic distribution of PPNs in agricultural systems. Recent studies show that rising temperatures accelerate nematode development, increasing the number of generations within a production season and facilitating the spread of many economically important species toward higher latitudes and elevations. Changes in precipitation patterns and soil moisture directly affect nematode survival, mobility, and infection success, and these effects often vary depending on regional conditions and nematode species. Elevated atmospheric CO₂ levels modify plant–nematode interactions by increasing root biomass, altering rhizosphere processes, and regulating plant defense pathways (e.g., jasmonic acid and salicylic acid signaling), which may enhance host susceptibility and infection intensity. Furthermore, extreme climate events can disrupt the natural balance in soil ecosystems, weakening natural antagonist–nematode relationships. However, responses of PPNs to climate change are not uniform, and contrasting findings across studies indicate that these responses are strongly shaped by species-specific traits and environmental variability. In addition, future research should focus on long-term and multi-factorial field studies to better capture the combined effects of climate drivers. Overall, climate change is expected to increase PPN prevalence and drive shifts in their geographic distribution, highlighting the need for climate-sensitive and regionally adapted nematode management strategies. Full article

(This article belongs to the Special Issue Plant Pathology and Nematology)

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14 pages, 1492 KB

Open AccessArticle

Validation of Guanidine-EDTA as a Preservative Agent for the Analysis of miRNAs and mRNAs in Blood Samples of Chagas Disease Patients

by Amanda Faier-Pereira, Paula Finamore-Araujo, Maria Mikaely Ribeiro Brito, Alejandro Marcel Hasslocher-Moreno and Otacilio C. Moreira

Pathogens 2026, 15(4), 424; https://doi.org/10.3390/pathogens15040424 - 14 Apr 2026

Viewed by 704

Abstract

Chagas disease (CD) is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi, representing a major socioeconomic challenge. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression, and several pathogens, including T. cruzi, can modulate host miRNA [...] Read more.

Chagas disease (CD) is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi, representing a major socioeconomic challenge. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression, and several pathogens, including T. cruzi, can modulate host miRNA networks. In this context, we hypothesized that host-derived miRNAs could serve as biomarkers in chronic CD. Given the intrinsic lability of RNA, we evaluated the efficacy of a 6 M guanidine-HCl/0.2 M EDTA solution, widely used in the molecular detection of T. cruzi DNA, in preserving mRNAs and miRNAs when mixed in a 1:1 ratio with human blood. Samples with or without guanidine were enriched with exogenous miRNAs (cel-miR-39 and cel-miR-54) and stored at 4 °C. RNase P expression was also evaluated in blood samples stored for up to 120 days and in samples from patients with CD, allowing direct comparison of mRNA stability over time. Samples preserved with guanidine-EDTA showed Ct values that were 4 to 5 cycles lower for all targets analyzed and demonstrated greater RNA stability over time. Taken together, these findings demonstrate that guanidine-EDTA robustly preserves mRNA and miRNAs in human blood, expanding the feasibility of molecular analyses in retrospective samples and corroborating its potential application in the studies of biomarkers of therapeutic response and prognosis in CD. Full article

(This article belongs to the Special Issue Diagnosis, Prevention, and Treatment of Leishmaniasis and Chagas Disease: Focus on Latin American Context)

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21 pages, 734 KB

Open AccessReview

Inflammation and RONS Dysregulation by Redox Enzymes as Mechanistic Links in HIV-1–Cancer Comorbidity

by Charles Gotuaco Ang, Shreya Eyunni and Irwin M. Chaiken

Pathogens 2026, 15(4), 423; https://doi.org/10.3390/pathogens15040423 - 14 Apr 2026

Viewed by 865

Abstract

Antiretroviral therapy (ART) effectively controls Human Immunodeficiency Virus Type-1 (HIV-1) infection in people with HIV-1 (PWH), preventing the progression of their infections to AIDS. However, as PWH age, they experience lifestyle- and age-related diseases, notably various types of cancer beyond those traditionally associated [...] Read more.

Antiretroviral therapy (ART) effectively controls Human Immunodeficiency Virus Type-1 (HIV-1) infection in people with HIV-1 (PWH), preventing the progression of their infections to AIDS. However, as PWH age, they experience lifestyle- and age-related diseases, notably various types of cancer beyond those traditionally associated with AIDS, with greater incidence and mortality than their non-HIV-1-positive counterparts, despite effective arrest of HIV-1 infection by ART. Dysregulation of redox enzymes presents an underexplored linkage between HIV-1 infection and cancer comorbidity, impacting reactive oxygen/nitrogen species (RONS) management, inflammation, immune function, and mitochondrial function. Chronic HIV-1 infection increases both RONS production and RONS neutralization responses, accelerating development of a sustained RONS-rich environment that still possesses sufficient dampening to prevent outright cytotoxic effects. Such an environment promotes both tumor proliferation and resistance adaptations to chemo- and radiotherapies. This review considers the effects of chronic HIV-1 infection on redox enzyme function and links these effects to tumorigenic mechanisms as potentially shared pathways. We then examine current methods of modulating redox function, consider how these could potentially impact both HIV-1 infection and cancer progression, and lastly propose future methods of co-treatment that could be explored. Full article

(This article belongs to the Section Viral Pathogens)

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25 pages, 1805 KB

Open AccessReview

Polyamines as Gatekeepers of Virus Replication and Central Nervous System Homeostasis

by Samantha P. Stacey and Bryan C. Mounce

Pathogens 2026, 15(4), 422; https://doi.org/10.3390/pathogens15040422 - 14 Apr 2026

Viewed by 914

Abstract

Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are [...] Read more.

Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are necessary for proper neuronal differentiation and memory formation, their dysregulation is a hallmark of neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases. Neurotropic viruses, including poliovirus, Zika virus, and human cytomegalovirus are significant human pathogens that rely on cellular metabolites for their replication, including polyamines. These pathogens exploit polyamines at multiple stages of their life cycles, relying on them for virion stability, cellular attachment, and the stimulation of viral enzyme activity. Notably, diverse viral families share this dependence, making polyamine biosynthesis a prime target for broad-spectrum antiviral therapies. This review covers the current understanding of polyamine metabolism in virus infection and CNS health and disease, as well as considering antiviral therapies targeting host polyamines to limit neurotropic virus infection. Full article

(This article belongs to the Special Issue Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics)

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