Pathogens最新文献

Chronic arthritis following arthritogenic alphavirus infections presents symptoms resembling autoimmune rheumatic diseases, raising questions about the underlying mechanisms, including molecular mimicry and autoantibody production. This systematic review evaluated evidence supporting molecular mimicry and the potential role of autoantibodies as predictive biomarkers in alphavirus-induced chronic arthritis. A comprehensive search of PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines and PECO framework. Thirteen studies met the inclusion criteria: four computational studies assessing peptide homology between viral and human proteins, and nine clinical studies evaluating autoantibodies in chronic post-alphavirus arthritis. Computational analyses identified conserved alphavirus peptides with sequence and structural similarity to human proteins implicated in autoimmunity, supporting the hypothesis of molecular mimicry. However, most lacked experimental validation. Clinical studies showed variable detection of autoantibodies, rheumatoid factors, anti-cyclic citrullinated peptide, and antinuclear antibodies in chronic patients, though seropositivity rates were inconsistent and generally low. Only one study reported a significant association between autoantibody levels and disease chronicity. The findings suggest a potential autoimmune component in post-alphavirus arthritis driven by molecular mimicry, though current evidence remains inconclusive due to methodological heterogeneity and limited validation. Autoantibodies may contribute to pathogenesis but are not reliable predictors of chronicity. Future longitudinal studies with standardized assays and validation of computational findings in human models are needed.

Vultures are extraordinarily adapted to feed on carrion, providing them with a constant microbiologically hostile environment. This peculiar ecological position has influenced the evolution of their gut microbiota, potentially conferring its uncommon antimicrobial traits and resistance to stress. In this study, we report on the isolation and comprehensive characterization of a lactic acid bacterium strain, identified as Ligilactobacillus agilis, from vulture feces via 16S rRNA gene sequencing. This strain exhibited potent antagonistic activity against several clinically relevant bacterial pathogens, including Salmonella enterica Typhimurium (25.26 ± 0.26 mm), Escherichia coli (23.5 ± 0.88 mm), Staphylococcus aureus (23.1 ± 1.8 mm), and Listeria monocytogenes (24.88 ± 0.61 mm), as demonstrated by agar well diffusion assays. Remarkably, it also demonstrated considerable resilience in simulated gastrointestinal conditions, with survival rates of 52.5 ± 7.4% in artificial gastric juice and 61.1 ± 3.7% in intestinal fluids. Antimicrobial susceptibility profiling confirmed its sensitivity to a broad range of commonly used antibiotics, including gentamicin, streptomycin, clindamycin, and penicillin. Whole-genome sequencing further revealed a complete repertoire of core genes associated with genetic information processing, robust carbohydrate metabolism, and nutrient assimilation, underscoring its adaptability and probiotic potential. It is important to note that the analysis of the assembled genome against VFDB did not show the presence of any known virulence factor according to the given criteria, which is preliminary evidence of safety-related aspects that are to be followed with the help of guideline-based analyses. Taken together, the unique ecological origin and in vitro inhibitory activity against the tested pathogens, gastrointestinal robustness, genomic features, and safety credentials position this L. agilis strain as a promising probiotic candidate for mitigating enteric infections in animal production systems, warranting further functional validation and in vivo efficacy studies.

L. infantum and L. donovani, distinct species in the L. donovani complex, show high phenotypic and genotypic polymorphism and share molecular traits. Therefore, genotyping by a single molecular target can give uncertain results. This study focuses on genotyping a set of L. donovani complex strains, including 18 zymodemes classified according to Montpellier nomenclature (ZMONs) and different clinical forms, by internal transcribed spacer (ITS), heat shock protein 70 (hsp70), and cysteine proteinase b (cpb) sequencing to evaluate their ability in species discrimination. We found an unexpected L. infantum hsp70 variability, with 8 sequence variants. Cpb-PCR could not distinguish L. donovani complex species, due to a L. infantum intraspecific allelic (cpbEF) polymorphism. By combining ITS-hsp70-cpb sequence variants, we obtained different genotypes. ITS(A)-hsp70inf(2)-cpbE identified 69.9% of L. infantum strains representing 12 ZMONs from Mediterranean visceral and cutaneous cases, ITS(A)-hsp70inf(2)-cpbF identified a non-ZMON-1 cluster. Four genotypes represented ZMON-24: ITS(A, B)-hsp70(Y)-cpbF identified a cutaneous cluster from Italy and North Africa, ITS(A, Lombardi)-hsp70(2)-cpbE identified cutaneous and visceral cases from Mediterranean areas. We believe this study contributes to an overview of L. infantum variant populations, and to the discussion on diagnostic targets, in single or multi -target-based approaches, to identify Leishmania populations in the Mediterranean area.

Choledochal cyst (CC), a congenital biliary anomaly, is associated with recurrent infections, chronic inflammation, and an increased risk of malignancy. Although emerging evidence implicates the biliary microbiome in disease pathophysiology, its developmental dynamics in pediatric CC remain unclear. Using deep metagenomic sequencing and comprehensive functional annotation, this study characterized age-dependent changes in the biliary microbiome of 201 pediatric CC patients stratified into infancy (<1 year), early childhood (1-5 years), and later childhood (5-12 years). We found that while the taxonomic composition and alpha diversity of the microbiota remained conserved across age groups, profound functional remodeling occurred with host development. A core set of microbial species(Bacteroidota, Actinomycetota, Bacillota, and Pseudomonadota) and functional pathways was shared across all ages; however, early childhood (1-5 years) exhibited the greatest number of unique functional genes, metabolic pathways, and carbohydrate-active enzymes, identifying this period as a critical window for microbial metabolic adaptation. Age-specific patterns were also evident in clinically relevant traits: infants (<1 year) harbored the most unique antibiotic resistance and virulence factor genes, whereas the resistome and virulome became more streamlined in older children. These findings establish a paradigm of "taxonomic conservation coupled with functional remodeling" in the CC microbiome and highlight age as a key determinant of microbial community function. This study offers novel insights into the microbial dynamics underlying CC progression and suggests potential age-specific targets for future therapeutic strategies.

Candidatus Rickettsia colombiensis is a new candidate species of Rickettsiae spotted fever group that have been isolated only from ticks. The pathogenicity of Ca. R. colombiensis to human and animals is unknown. This study evaluated the pathogenic potential of Ca. R. colombiensis in Syrian hamsters and assessed the cross-reactivity between Ca. R. colombiensis and other Rickettsia in human and hamster sera. Shell vial technique was employed to isolate Ca. R. colombiensis. Subsequently, five male Syrian hamsters were inoculated intraperitoneally (IP) and five intradermally (ID) with 1 × 10⁶ Vero cells infected with Ca. R. colombiensis. One control hamster was used in each group. The health status was assessed daily, and necropsies were performed. Serum samples were tested by indirect immunofluorescence and tissues were processed by qPCR and histological stains. All Syrian hamsters remained healthy during the trial. No histopathological damages associated with rickettsial infection were observed. No Rickettsial DNA was detected in tissues. Syrian hamsters showed IgG antibody titers ranging from 1:64 to 1:1024. Control hamsters were negative. Regarding human sera, 56% (84/150) had IgG cross-reactivity antibodies against Ca. R. colombiensis. Subsequently, in a selected subset of 30 sera with moderate to high titers, all samples reacted with Ca. R. colombiensis antigen. Under specific conditions of this study, Ca. R. colombiensis did not behave as a highly virulent pathogen in the hamster model, although all infected Syrian hamsters developed IgG antibodies responses. Regarding cross-reactivity, it is possible to serologically diagnose rickettsial infection using Ca. R. colombiensis as an antigen.

Recently, a new species, Serratia sarumanii, was described, belonging to a group of strains previously identified as Serratia marcescens in routine clinical analyses. It was shown that the identification of S. marcescens isolates by biochemical testing, mass spectrometry, or 16S rRNA gene sequencing was insufficient to resolve the 'S. marcescens complex', while sampling point analysis revealed that many genomes assigned to the S. sarumanii cluster were associated with a clinical context. Thus, here the clinical relevance and local as well as global distribution of S. sarumanii is analyzed. In total, 21 strains from three hospitals in Eastern Westphalia-Lippe (OWL), previously identified as S. marcescens and potential causative agents from severe bacterial infections, were analyzed by genome sequencing and species identification. It could be shown that only one isolate was confirmed as S. marcescens, whereas 10 of the 21 isolates were identified as S. sarumanii, indicating that S. sarumanii is the dominant representative of the "Serratia marcescens" complex in hospitals in OWL. To analyze the global species distribution, all Serratia genomes available in GenBank were reclassified. About one-third of these genomes were identified as S. sarumanii, indicating S. sarumanii as the most dominant Serratia species in clinical settings around the world.

Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, a burden further exacerbated by HIV co-infection and the increasing prevalence of drug-resistant strains. Although a wide range of laboratory diagnostic methods are currently available, their applicability, implementation, and clinical impact vary substantially across healthcare settings with different levels of complexity and resources. This review provides a comprehensive overview of the main laboratory diagnostic methods for active and latent TB, emphasizing their clinical applicability, implementation challenges, and role within integrated diagnostic strategies. Conventional approaches, such as smear microscopy and culture, are discussed alongside modern diagnostic technologies, including automated nucleic acid amplification tests (NAATs), loop-mediated isothermal amplification (LAMP), line probe assays (LPAs), next-generation sequencing (NGS), and lateral flow assays, highlighting their strengths and limitations in distinct epidemiological and operational contexts. Unlike existing WHO guidelines and prior reviews that predominantly focus on test performance and recommendation status, this review adopts an implementation-oriented perspective, critically examining diagnostic methods in light of real-world constraints, regional disparities, and evidence gaps. Particular attention is given to limitations related to laboratory infrastructure, biosafety, workforce capacity, and sustainability, as well as to under-addressed areas such as latent TB, metagenomic approaches, and the investigation of co-pathogens. By integrating WHO guidance with contextual and operational considerations, this review aims to support rational test selection and the development of flexible, integrated diagnostic workflows tailored to local health system capacity, patient populations, and clinical scenarios, thereby strengthening the effectiveness and equity of TB diagnostic strategies.

Visceral leishmaniasis (VL) is an endemic zoonotic disease in southern Europe with increasing clinical relevance among immunocompromised populations; however, detailed clinical data remain scarce. This retrospective multicentre cohort study analysed patients with confirmed VL treated at seven hospitals in Greece over a 26-year period. Clinical, treatment, and outcome data were collected with a minimum follow-up of 18 months to assess cure, treatment failure, relapse, and mortality. A total of 144 patients were enrolled (59% male; mean age 41.8 years, range 0.1-84 years), most of whom were Greek nationals (85%) and resided in rural areas (61%). Fever was the primary reason for hospital admission in 95% of patients. At diagnosis, 42 patients (29%) were immunocompromised. These patients were significantly older than immunocompetent individuals and more likely to present with diarrhoea and arthralgia, whereas hepatomegaly was less frequent. Liposomal amphotericin B was administered to 90% of patients. Treatment failure occurred in 14 patients (10%) and was significantly associated with immunosuppression and leukaemia. Relapse within 18 months occurred in 5.5% of patients. Overall mortality was relatively low (7 patients, 5%), with one death directly attributable to VL. This study demonstrates that VL remains endemic in Greece, affects patients across all age groups, and is primarily autochthonous. Immunosuppression is associated with distinct clinical features and poorer treatment outcomes in VL, underscoring the need for heightened clinical vigilance, combined diagnostic approaches, and extended follow-up in vulnerable populations.

Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging pathogen responsible for healthcare-associated infections. For this reason, 44 VREfm isolates collected during 2021-2023 were characterized using phenotypic and genomic approaches. VREfm isolates were identified by MALDI-TOF and antimicrobial susceptibility tests were performed with Vitek 2, Sensititre, or E-test. Sequence type (ST), antibiotic resistance genes, virulence factors and genetic relatedness were determined using Next Generation Sequencing. Forty-three isolates had a VanA phenotype and vanHAX genotype and one had a VanB phenotype and vanHBX genotype. Isolates showed high antibiotic resistance to various antibiotics, but generally remained susceptible to quinupristin/dalfopristin, tigecycline and eravacycline. Two isolates were resistant to linezolid, showing the chromosomal mutation G2576T in domain V of the 23S rRNA gene in one isolate, and the transferable linezolid resistance genes cfr(D) and optrA in the other. Thirty-eight isolates belonged to ST80, one to ST17 (ST80 and ST17 are included in CC17) and one to ST697. Genomic analysis of the ST80 isolates showed that nearly all of them belonged to a single cluster. To prevent further spread of VREfm in the nosocomial environment, in addition to the application of up-to-date infection control strategies and antibiotic stewardship programs, the implementation of genomic surveillance is recommended.

The use of antiretroviral therapy (ART) as the only effective way to control human immunodeficiency virus (HIV) infection results in HIV drug resistance. Next-generation sequencing (NGS) has become a common method for identifying drug-resistant variants and reducing analysis costs. The aim of this study was to develop an NGS-based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024-2025. Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using NGS. HIV-1 drug resistance analysis was conducted using the Stanford University HIVdb database. CXCR4 cell tropism was predicted using an empirical rule classifier. A protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. High levels of resistance were observed to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced patients and to NNRTIs in treatment-naïve patients. Low levels of resistance were observed to protease and integrase strand transfer inhibitors (INSTIs). CXCR4 cell tropism was extremely rare. NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS-based protocols allows for performing ART efficiency and tropism monitoring at scale.