Search Results (2,347)

Staphylococcus pseudintermedius is a common opportunistic pathogen in companion animals and a leading cause of skin and soft tissue infections (SSTIs). Despite its clinical relevance, the genomic determinants underlying pathogenicity and the transition from commensal carriage to invasive infection remain poorly understood. This study aimed to identify the genomic determinants of SSTI pathogenic potential in S. pseudintermedius and to determine whether pathogenicity is driven by single, major-effect virulence genes or by polygenic genome-wide genetic architecture. Using accessory gene-based and unitig-based genome-wide association studies (GWASs), employing a linear mixed model, across a genetically diverse collection of S. pseudintermedius isolates spanning multiple phylogenetic clades, we found that disease and carriage isolates showed no phylogenetic clustering. SSTI pathogenicity exhibited high narrow-sense heritability. Surface-associated LPXTG-anchored proteins, particularly spsF, harbored the strongest associations, with additional signals in iron metabolism (narH, sufB) and oxidative stress tolerance (ahpC). Random Forest classification validated GWAS signals. SSTI pathogenicity in S. pseudintermedius reflects a polygenic architecture driven by cumulative variation across surface-associated, metabolic, and stress-response loci, shifting focus from single virulence genes to genome-wide genetic variation. Full article

Despite extensive research, the complex relationship between cellular senescence, aging, and host–pathogen interactions remains incompletely understood. This paper aims to review cellular and molecular alterations of senescent cells and critically examine the role of bacterial infections as key drivers in immunosenescence. Molecular mechanisms underlying pathogen-induced stress responses and the subsequent impact on host tissues and immune function are also highlighted. The novelty of this work lies in integrating current knowledge into direct and indirect mechanisms by which bacterial pathogens induce senescence, including genotoxic effects, oxidative stress, and disruption of host signaling pathways. Particular emphasis is placed on how bacterial virulence factors modulate critical pathways such as p53–p21, p16^INK4a–Rb, NF-κB, mTOR, and cGAS–STING, thereby promoting a pro-inflammatory senescence-associated secretory phenotype (SASP) and facilitating chronic infection and tissue damage. By linking microbial activity with cellular aging processes, this work offers a novel perspective on the contribution of infections to premature aging and age-related diseases and highlights potential therapeutic targets for modulating senescence and improving host resilience. Full article

Background/Objectives: Streptococcus agalactiae is one of the most significant pathogens causing infections in humans and mastitis in dairy cattle. This work focused on a comprehensive comparative pan-genomic analysis of bovine and human Group B Streptococcus to elucidate the genetic mechanisms underlying host adaptation and dissemination. Methods: Isolates of S. agalactiae from quarter milk samples from dairy herds in Lombardy (Italy), along with human strains, were considered. Whole genome sequencing was used to compare core and accessory genomes, assign sequence types, and find virulence and resistance factors. Results: 30 sequence types were detected, of which two (ST12 and ST23) in common between bovine and human. The allele frequencies for resistance determinants revealed elevated rates for tetM (59.8% overall, 66.5% in human clinical isolates), ermB (17.3% overall, 20.4% in human clinical isolates), and ant(6)la (8.9% overall, 12.8% in human clinical isolates). Bovine strains had accessory gene clusters linked to lactose metabolism and immunological evasion, whereas human isolates were concentrated in regions related to adhesion and antibiotic resistance. Conclusions: Comparative pan-genomics show that there is a small genetic overlap between bovine and human Group B Streptococcus populations. Full article

Background: Periodontitis is increasingly recognised as a significant risk factor for adverse pregnancy outcomes (APOs), yet the mechanisms by which oral pathogens trigger placental dysfunction remain unclear. Porphyromonas gingivalis (Pg), a keystone periodontal pathogen, secretes outer membrane vesicles (Pg-OMVs) that carry virulence factors and can reach distant organs. However, the impact of Pg-OMVs on placental trophoblasts and the accompanying metabolic disturbances is poorly understood. This study investigated the effects of Pg-OMVs on trophoblast function and metabolism. Methods: Pg-OMVs were isolated from Pg cultures. Pregnant mice were exposed to Pg-OMVs in vivo, and placental and uterine weights were recorded. Human trophoblast cells were treated with Pg-OMV in vitro. Untargeted metabolomic profiling of placental tissues was conducted using liquid chromatography–mass spectrometry. Fatty acid β-oxidation (FAO) activity, CD36 expression, and mitochondrial integrity were assessed via enzymatic assays, immunoblotting, transmission electron microscopy, mitochondrial membrane potential measurements, and oxygen consumption rate analysis. Results: Pg-OMVs were internalised by placental trophoblasts, and their presence was associated with significantly reduced placental and uterine weights. Metabolomics revealed a marked accumulation of long-chain acylcarnitines, particularly C20:1 carnitine, indicating impaired FAO. Pg-OMV exposure suppressed FAO activity, downregulated the fatty acid translocase CD36, and induced severe mitochondrial dysfunction, evidenced by cristae loss, decreased mitochondrial membrane potential, and diminished oxygen consumption rates. Conclusions: Pg-OMV compromise placental integrity by disrupting mitochondrial fatty acid β-oxidation, providing a novel mechanistic link between periodontal pathogen-derived vesicles and the pathogenesis of APOs. Full article

Extraintestinal pathogenic Escherichia coli (ExPEC) causes severe infections in humans and animals, yet bovine isolates remain poorly characterized. Here, we report the first complete genome of a bovine ExPEC strain, BN01 (serotype O101:H9-ST10-phylogroup A), isolated from calf meningoencephalitis. Unlike classical ExPEC that typically belong to B2/D phylogroups and O1/O2/O18 serotypes, BN01 represents the A-ST10-O101 sublineage that has emerged as predominant among bovine ExPEC populations. The genome comprises a chromosome encoding 197 virulence factors, with cdiA uniquely identified in BN01 compared to six other representative ExPEC genomes—a contact-dependent growth inhibition system, and three distinct plasmids: a conjugative ESBL carrier (blaCTX-M-164, IncI1), a bovine-associated multidrug resistance island (IncY), and a mobilization-ready vector (IncFII). Animal virulence assays demonstrated that intraperitoneal challenge with E. coli BN01 caused 80% mortality (8/10 mice) within the observation period and yielded an LD₅₀ of 10^6.3 CFU/mouse. These findings demonstrate that high-risk ExPEC can occur in phylogroups typically associated with commensal strains, expanding the conventional understanding of phylogroup–virulence associations. They highlight the need to assess the zoonotic potential of livestock-associated atypical lineages and support integrated genomic surveillance under the One Health framework. Full article

Elizabethkingia species have emerged as important nosocomial pathogens associated with multidrug resistance and persistent infections. This study aimed to characterize clinical Elizabethkingia isolates from Northern Thailand regarding antimicrobial susceptibility, virulence-associated phenotypes, and biofilm formation, and to evaluate the antimicrobial and anti-biofilm activity of dialdehyde cellulose (DAC) film. A total of 49 clinical isolates were identified by MALDI-TOF mass spectrometry, with species identification confirmed by 16S rRNA gene sequencing. Antimicrobial susceptibility was determined against 12 agents. Virulence traits (protease, lipase, lecithinase, and hemolysin production) and biofilm formation were assessed using standard phenotypic assays. DAC films were evaluated against selected resistant isolates. Elizabethkingia anophelis predominated, and most isolates exhibited multidrug or extensive drug resistance, with high resistance to carbapenems and cephalosporins. Piperacillin–tazobactam, levofloxacin, and trimethoprim–sulfamethoxazole showed the greatest activity. All isolates demonstrated protease production and time-dependent hemolysis, while lipase and lecithinase activities were absent. Biofilm formation varied among isolates, while DAC films inhibited bacterial growth and prevented detectable biofilm formation in the tested isolates. No significant difference was observed between DAC and DAC supplemented with meropenem in inhibition zone diameters (p = 0.555). Clinical Elizabethkingia isolates demonstrated extensive antimicrobial resistance with conserved virulence traits and heterogeneous biofilm formation. DAC films demonstrated antimicrobial activity and prevented detectable biofilm formation under the experimental conditions. Further studies are warranted to evaluate their mechanism of action and potential applications. Full article

Zymoseptoria tritici (Desm. Quaedvlieg & Crous), known as the wheat leaf spot disease agent, is a highly virulent fungus that induces blotch and necrosis on leaves. Although it is known to cause severe infections under humid conditions, recent observations suggest that it can also infect wheat leaves under drought and high-temperature conditions, possibly influenced by global warming. Recent findings showed that Z. tritici could easily tolerate various abiotic stresses, including drought, water stress, salinity, and temperature. It has been evident that the fungus can tolerate pesticide stress, as indicated by the increased frequency and number of pesticide applications throughout the growing season. Under stress conditions, the fungi, unlike crop plants, could easily tolerate stress by rapidly modifying gene expression and reducing spore production and mycelial growth without downregulating major biochemical components that play significant roles in pathogenicity and virulence. Z. tritici can accumulate melanin under stress conditions; therefore, an increase in pathogenicity under drought or salinity stress is not unexpected. Recent studies have shown that the pathogenicity of the fungus is increasing, and more virulent, toxin-producing pathogens might emerge in the future. Since drought and high-temperature stresses significantly affect crop plants, the adaptation of pathogenic microorganisms to these conditions could be inevitable if abiotic stress persists. Under these circumstances, the crop loss would be more pronounced. A critical aspect of this process is the assessment of DNA integrity in both wheat and the pathogen under drought stress conditions. The organism that better maintains DNA integrity is considered to exhibit greater drought tolerance. Therefore, our main target should be DNA health when developing or breeding new wheat varieties, considering double- or even multiple-stress conditions. We should finally state that we are very optimistic about generating highly stress-tolerant wheat varieties via metabolomic and proteomic approaches without compromising quality. However, the impact and combination of stress factors are becoming increasingly complex. Full article

Diarrheal disease remains a significant public health concern in Bhutan; however, the genomic epidemiology of the circulating diarrhoeagenic Escherichia coli (DEC) strain remains poorly understood. This study characterized the genomic diversity, antimicrobial resistance (AMR), and virulence determinants of DEC isolates using whole-genome sequencing (WGS). DEC isolates recovered from stool samples and collected through Bhutan’s National Diarrheal Disease Surveillance sentinel hospitals during 2023 were identified by a multiplex polymerase chain reaction, tested for antimicrobial susceptibility using the Kirby–Bauer disc diffusion method, and sequenced on the Illumina MiSeq platform. Genomes were analyzed using the Bohra pipeline to determine pathotypes, phylogeny, multilocus sequence types, serotypes, virulence factors, and AMR genes. Of the 29 DEC isolates, 27 were confirmed by WGS and enteropathogenic E. coli (37.0%) and enteroaggregative E. coli (33.3%) were the predominant pathotypes. Isolates exhibited extensive genetic diversity, representing phylogroups A and B1 and 22 serotypes. Phenotypic resistance to β-lactams was common, with 25.9% of isolates carrying bla_CTX-M-15. Virulence profiling identified diverse adhesins, toxins, iron acquisition systems, and type III secretion system components. DEC isolates in Bhutan comprise a genetically diverse population with a concerning convergence of virulence determinants and multidrug resistance. The findings underscore the strengthening of sustained genomic surveillance to monitor AMR and genomic epidemiology of bacterial pathogens. Full article

Porcine diarrheagenic Escherichia coli strains exhibit heterogeneous virulence profiles involving multiple factors, complicating broad-spectrum serological diagnosis. Here, we designed a multiepitope fusion antigen, MEAET, containing predicted B-cell epitopes from six major virulence factors, K88/F4, F18, LT, Stx2e, HlyA, and Tir, and developed an indirect ELISA for broad antibody detection. Structural modeling predicted a well-folded conformation with multiple discontinuous B-cell epitopes, and molecular docking suggested favorable interactions between the C-terminal dendritic cell-targeting peptide and the porcine immune receptor SLA1. Immunization of piglets with purified recombinant MEAET generated hyperimmune serum with a titer exceeding 1:102,400, which specifically recognized all six individual antigens by Western blot. The optimized ELISA demonstrated satisfactory repeatability (intra-assay CV ≤ 4.26%) and reproducibility (inter-assay CV ≤ 5.57%), showed no detectable cross-reactivity with antibodies against other tested porcine pathogens, and exhibited good analytical sensitivity, with positive sera detectable at dilutions up to 1:3200. The optimized ELISA showed good repeatability and reproducibility, with intra-assay and inter-assay coefficients of variation of ≤4.26% and ≤5.57%, respectively, no detectable cross-reactivity with the tested heterologous controls, and good analytical sensitivity, with positive sera remaining detectable at dilutions up to 1:3200. The S/P ratio cut-off was 0.203. In field sera, positivity rates were 74.5% (35/47) in diarrheic pigs and 34.0% (36/106) in asymptomatic pigs. These primary results indicate that the MEAET-based indirect ELISA represents a promising tool for serological detection of antibodies against multiple virulence factors of diarrheagenic E. coli in pigs and for field surveillance in swine herds. Full article

Plant-pathogenic bacteria threaten crop productivity and quality, yet chemical options remain limited compared with those for fungal and oomycete diseases. Current management relies mainly on copper bactericides, limited antibiotics, induced-resistance agents, biocontrol and resistant cultivars. However, copper and streptomycin resistance, efflux-mediated multidrug tolerance and rapid pathogen adaptation have weakened these strategies. Target-oriented research provides a framework for exploring agricultural antibacterials, anti-virulence agents, anti-colonization strategies, resistance sensitizers and host-resistance interventions, but many of these approaches remain conceptual, model-system, greenhouse or medical-bacteriology-derived rather than proven field solutions. This review classifies bacterial control targets into two interconnected groups: growth-essential targets, including peptidoglycan biosynthesis, membrane/envelope systems, nucleic-acid processes, protein synthesis, metabolism, nutrient transport and cell division; and anti-virulence/anti-adaptation targets, including secretion systems, quorum sensing, biofilms, motility, adhesion, cell-wall-degrading enzymes, tolerance systems, oxidative-stress responses and host susceptibility factors. Using “Candidatus Liberibacter asiaticus” (CLas) as a case study, genome annotation and infection-stage transcript-abundance data prioritized Sec-dependent secretion, outer-membrane/surface proteins, Bam assembly, nutrient transporters, Clp proteostasis, redox adaptation and core cellular processes as candidate target classes. Envelope-associated, secretion/anti-virulence, nutrient-acquisition and stress-sensitization modules may represent potential directions for downstream validation, but CLas candidates remain hypothesis-generating priorities requiring validation for essentiality, conservation, druggability, delivery feasibility, crop safety and field performance. Full article

Non-aeruginosa Pseudomonas (NAP) species represent a diverse and ubiquitous group of Gram-negative bacteria inhabiting a wide range of environmental niches, from soil and water to plant rhizospheres and clinical settings. While Pseudomonas aeruginosa has historically dominated clinical and research focus, the significance of NAP species, such as Pseudomonas fluorescens, Pseudomonas putida, and Pseudomonas stutzeri, as both opportunistic human pathogens and versatile biotechnological agents is increasingly recognized. Their remarkable genomic plasticity, driven by large accessory genomes and mobile genetic elements, underpins their metabolic versatility and adaptability but also facilitates the acquisition of virulence determinants and antibiotic resistance genes, contributing to their emergence in healthcare settings, particularly among immunocompromised individuals. This review provides a comprehensive analysis of NAP species, focusing on recent advances in their taxonomy facilitated by genomic tools like Whole-Genome Sequencing (WGS) and Multilocus Sequence Typing (MLST), which reveal complex species groups and challenge traditional classifications. We delve into the genomic landscape, exploring pangenome dynamics, horizontal gene transfer (HGT), and the genomic signatures that may differentiate clinical from environmental isolates. The clinical relevance of NAPs is examined, detailing the spectrum of infections, epidemiological trends, risk factors, and insights into virulence mechanisms, including secretion systems (T3SS, T6SS) and pathogenicity islands. Addressing a critical need, this review incorporates detailed sections on the diagnostic challenges posed by NAPs, including common misidentifications and the role of modern techniques like MALDI-TOF MS and WGS, and outlines current and novel therapeutic strategies, considering the growing problem of antimicrobial resistance (AMR) within this group. Furthermore, the biotechnological applications of NAPs in bioremediation and biocatalysis are discussed alongside evolving biosafety considerations, reflecting the shift from strict containment to integrated monitoring approaches for genetically engineered strains. By synthesizing current knowledge and highlighting research gaps, this review underscores the necessity of integrated, One Health approaches to understand and manage the dual nature of non-aeruginosa Pseudomonas species as both environmental inhabitants and clinically relevant pathogens. Full article

Dermatophytosis is a cutaneous mycosis caused by keratinolytic fungi, classified as dermatophytes, affecting 20–25% of the global population and representing a significant public health concern. The disease manifests as circular, erythematous, pruritic, and desquamative skin lesions, hair breakage and loss, and nail degradation, leading to considerable morbidity. In addition, dermatophytosis can markedly impair patients’ quality of life. Despite the high global prevalence of dermatophytosis, the causative agents are often misdiagnosed, and there is limited data on the epidemiology and genomic surveillance of dermatophytosis worldwide. This review aims to update the global epidemiology of dermatophytosis and dermatophytes while addressing their taxonomy, pathogenesis, virulence factors, clinical manifestations, and antifungal therapy. Consistently, Trichophyton spp., particularly T. rubrum, T. mentagrophytes, and T. interdigitale, remain the predominant pathogens worldwide. Recently, T. indotineae has gained prominence due to its global dissemination, significant terbinafine resistance, extensive lesions, therapeutic failure, and recurrence. Furthermore, studies have reported endogenous cases of T. indotineae infections in Asia and Europe, and exogenous reports in the Americas and Oceania. Among non-Trichophyton dermatophytes, Microsporum canis and M. audouinii stand out as relevant pathogens, particularly in endemic regions and specific clinical settings, such as scalp infections. Overall, these factors emphasize the importance of global vigilance regarding dermatophyte dissemination. This review also highlights a discrepancy between accurate fungal identification and global reporting, raising concerns regarding epidemiological surveillance and underscoring the need for improved strategies to manage dermatophytosis worldwide. Full article

Helicobacter pylori possesses an unusually high number of restriction–modification (R-M) systems relative to its small genome, contributing to a methylome increasingly implicated in bacterial gene regulation. In this study, we analyzed the methylomes of two mutant strains of H. pylori 26695: ∆rdxA (control) and ∆rdxA/∆arsS. Each mutant was cultivated under neutral (pH 7) and acidic (pH 5) growth conditions. We identified one conspicuous hypomethylated region of 21 kBp possessing 21 annotated genes across each methylome. Notably, over 600 protein coding regions and 10 different promoters displayed differential methylation between pH conditions, including several virulence factors. The vacA gene, encoding the Vacuolating Cytotoxin A, exhibited eight differentially methylated positions between pH 7 and pH 5 within the H. pylori 26695 control mutant methylome, potentially contributing to its previously documented 32-fold down regulation of mRNA in acidic environments. pH-dependent methylation changes were widespread within the cag pathogenicity island, genes encoding cell envelope proteins including adhesin-encoding sabA, babA, and hopQ, and numerous flagellar-associated genes. These results reveal the plasticity of the H. pylori methylome and suggest that DNA methylation is responsive to environmental pH in both ArsRS-dependent and independent manners. Methylome dynamics may serve as an important layer of gene regulation in acclimation to hostile gastric environments and promote persistent infection. Full article

Background: Foodborne pathogenic Escherichia coli is a major public health concern due to its frequent association with meat and meat products and its potential to harbor virulence factors and antimicrobial resistance (AMR) determinants. Objective: This study aimed to investigate the prevalence, virulence gene profiles, and AMR patterns of E. coli isolates obtained from beef and chicken meat products. Methods: A total of 200 beef and chicken meat product samples were collected from retail markets in Samsun, Türkiye. Isolation of E. coli was performed using conventional culture-based methods, and PCR targeting the uspA gene was used for molecular confirmation. The presence of virulence genes (stx1, stx2, eae, and hlyA) was investigated by PCR. Antimicrobial susceptibility testing was conducted using the disk diffusion method, and multidrug resistance (MDR) and multiple antibiotic resistance (MAR) indices were evaluated. Results: Among the 200 samples analyzed, 80 (40%) were positive for E. coli, including 38 (38%) beef and 42 (42%) chicken meat samples. A total of 185 E. coli isolates were recovered and confirmed by PCR. Virulence gene analysis showed that stx2 was the most prevalent gene (51.4%), followed by eae (37.3%), hlyA (13.0%), and stx1 (6.5%). Antimicrobial susceptibility testing demonstrated high resistance rates to tetracycline (69.7%), ampicillin (58.4%), trimethoprim–sulfamethoxazole (48.1%), streptomycin (40.5%), nalidixic acid (40.0%), chloramphenicol (40.0%), and ciprofloxacin (34.1%). In contrast, the lowest resistance rates were observed for imipenem (2.2%), amoxicillin–clavulanate (4.9%), and amikacin (7.6%). Moreover, 126 isolates (68.1%) were identified as MDR, exhibiting resistance to at least three antimicrobial agents. The MAR index ranged from 0.06 to 1.00. Conclusions: The coexistence of virulence-associated genes and high AMR rates among E. coli isolates from meat products indicates a potential public health risk. These findings highlight the importance of continuous monitoring of pathogenic and antimicrobial-resistant E. coli throughout the food production chain. Full article

Disseminated human Lyme borreliosis is primarily associated with invasive spirochetes from the Borrelia burgdorferi sensu lato complex. Host–Borrelia interactions have been studied in a diverse range of vertebrate reservoirs. But despite the key role of the complement system in innate immunity, comparative studies evaluating the susceptibility of individual Borrelia species to human complement-mediated killing are limited. Using serum sensitivity assays, we analyzed complement-mediated killing of 10 B. burgdorferi s.l. genospecies in healthy individuals of different ages and sexes. The tested genospecies showed markedly different sensitivities to human complement. Statistical clustering divided the genospecies into three distinct groups based on whether their sensitivity to human complement was high, medium, or low. Complement resistance did not correlate with the recognized pathogenicity of the genospecies; species with unclear pathogenic potential exhibited resistance levels comparable to the major species causing human Lyme borreliosis, B. burgdorferi sensu stricto, B. afzelii and B. garinii. Females generally showed reduced complement-mediated killing compared to males. In addition, complement activity tended to decline with age, identifying host age and biological sex as important factors influencing the human innate immune response against Borrelia. Our findings suggest that the ability to evade human complement may be more widespread among Borrelia species than previously assumed. These results support an emerging model in which complement-mediated selection may shape host associations and transmission success without serving as an absolute predictor of Borrelia virulence. Full article