Virulence[JOURNAL]
Sun
200 papers
Effects of fecal microbiota transplantation and probiotics on the gut microbiome in antibiotic-treated septic patients: A pilot randomized controlled trial.
Chen Y, Zhao J, Zhao J … +10 more , Chen Q, Dong S, Jia S, Zhao Y, Hao D, Yin Y, Lin S, Chen Y, Zhuang Y, Peng H
Virulence · 2026 Dec · PMID 42174754 · Full text
Broad-spectrum antibiotics, essential for sepsis management in critically ill patients, cause significant gut dysbiosis. Restoring gut microbiota may improve outcomes, but the efficacy of interventions like fecal microbi...
Broad-spectrum antibiotics, essential for sepsis management in critically ill patients, cause significant gut dysbiosis. Restoring gut microbiota may improve outcomes, but the efficacy of interventions like fecal microbiota transplantation (FMT) and probiotics in this setting remains underexplored. This study aims to evaluate the feasibility and potential efficacy of FMT versus probiotics on gut microbiome restoration and inflammatory markers in critically ill, antibiotic-treated sepsis patients. In this single-center, prospective, exploratory pilot RCT, 40 sepsis patients were were randomized 2:1:1 to: Control ( = 20, antibiotics treatment), Probiotics ( = 10, antibiotics treatment combined one week of probiotics), and FMT ( = 10, antibiotics treatment combined one week of FMT) groups. Gut microbiota composition was analyzed using 16S rDNA sequencing, and clinical inflammatory markers were assessed at baseline, one week, and two weeks post-treatment. FMT significantly mitigated antibiotic-induced reductions in microbial diversity. At 2 weeks, the FMT group exhibited higher alpha-diversity (Chao1 index, = 0.0125; Shannon/Simpson trends = 0.06) compared to Control and Probiotics groups. FMT increased beneficial abundance and reduced . BugBase analysis revealed FMT significantly lowered pathogenic potential of gut microbiota ( = 0.021). Donor-recipient analysis showed FMT shifted recipient microbiomes toward donor enterotype. This study provides preliminary evidence that FMT, but not the probiotic regimen, effectively restores gut microbiome diversity and composition, reduces pathogenic potential, and may improve clinical outcomes in critically ill sepsis patients after broad-spectrum antibiotics. This study was registered on ClinicalTrials.gov (NCT05578196).
Immune discrimination between commensals and pathogenic bacteria.
Alanazi HH
Virulence · 2026 Dec · PMID 42173824 · Full text
Interaction with various bacteria is essential for the development of various components of the immune system. To prevent disease, the immune system must continuously discriminate between commensal and pathogenic bacteri...
Interaction with various bacteria is essential for the development of various components of the immune system. To prevent disease, the immune system must continuously discriminate between commensal and pathogenic bacteria. The immune system employs several mechanisms to discriminate between beneficial and harmful bacteria. This ensures selective immune tolerance toward commensals, especially in the gastrointestinal tract. Both commensal and pathogenic bacteria contain features that provoke immune responses. However, how the immune system reacts to or eliminates bacterial infections while preserving commensals is not fully understood. This review aims to explore the underlying mechanisms used by the immune system to distinguish between commensals and pathogenic bacteria. The review also addresses how commensals interact with immune system components to facilitate immune discrimination and host protection. Finally, dysbiosis and therapeutic interventions used to restore microbial balance are also discussed in this review.
FGF8-mediated TRIM16 regulation promotes K48-linked ubiquitination and degradation of RIG-I to facilitate Influenza a virus immune evasion.
Wei R, Zhang H, Cheng K … +4 more , Wang S, Yuan Z, Ma S, Yu Z
Virulence · 2026 Dec · PMID 42171628 · Full text
Influenza A virus (IAV) exhibits notable genetic diversity and cross-species transmission capacity, posing a continuous challenge to public health. Elucidating host immune regulatory mechanisms is crucial for identifying...
Influenza A virus (IAV) exhibits notable genetic diversity and cross-species transmission capacity, posing a continuous challenge to public health. Elucidating host immune regulatory mechanisms is crucial for identifying new antiviral targets that can overcome viral resistance. Here, using human A549 lung epithelial cells as the primary model, we identify fibroblast growth factor 8 (FGF8) as a crucial host factor whose expression is significantly elevated during infection by various IAV subtypes (including H1N1, H13N2, H9N2, and PR8). Through gain- and loss-of-function assays, we demonstrate that FGF8 specifically enhances viral replication at the post-entry stage by suppressing interferon-beta (IFN-β) and interferon-stimulated genes (ISGs) expression. Mechanistically, FGF8 reduces retinoic acid-inducible gene I (RIG-I) protein stability via K48-linked polyubiquitination without affecting its mRNA levels. Ubiquitination identifies Lysine 258 (K258) on RIG-I as the essential modification site; notably, a K258R mutation prevents RIG-I degradation and restores IFN-β induction. Furthermore, TurboID-based proximity labeling captures the close spatial association of FGF8 with both tripartite motif containing 16 (TRIM16) and RIG-I, revealing that FGF8 acts as a molecular scaffold to recruit the E3 ligase TRIM16 to RIG-I. Consistently, TRIM16 silencing replicates the antiviral effects of FGF8 knockdown. Collectively, our findings demonstrate that FGF8 recruits TRIM16 to degrade RIG-I, thereby facilitating viral immune evasion. Disrupting this interaction offers a potential avenue for anti-influenza A virus intervention.
Genomic epidemiological patterns and antifungal resistance profiles of in China: Spatiotemporal dynamics and persistent colonization.
Cao J, Wang XY, Qin C … +4 more , Gu D, Zhang R, Zhou H, Li R
Virulence · 2026 Dec · PMID 42171600 · Full text
() is an emerging multidrug-resistant fungal pathogen with major global public health implications. However, the clinical characteristics, clade-specific genomic variation, resistance-associated SNP patterns, and transmi...
() is an emerging multidrug-resistant fungal pathogen with major global public health implications. However, the clinical characteristics, clade-specific genomic variation, resistance-associated SNP patterns, and transmission dynamics of in China remain insufficiently understood. We retrospectively analyzed clinical data from 22 intensive care unit patients colonized or infected with and performed antifungal susceptibility testing and whole-genome sequencing (WGS) on 25 isolates. All isolates were resistant to fluconazole, and 80% were resistant to amphotericin B, whereas echinocandin susceptibility remained intact. Phylogenetic analysis assigned the isolates to Clade I ( = 19) and Clade III ( = 6). SNP analysis revealed marked clade-specific differentiation in resistance-associated genes, with Y132F enriched in Clade I and alterations, including VF125AL, enriched in Clade III. Additional variants in , , , and also showed clade-biased distributions and frequent co-occurrence. However, no significant association was observed between individual SNPs or mutation burden and antifungal susceptibility phenotypes. To investigate transmission dynamics, we conducted comparative genomic and phylogeographic analyses using 210 genomes. Major inbound introductions into China were inferred from Canada and South Korea to Guangdong and from Pakistan to Beijing, while phylogeographic modeling suggested that Beijing and Guangdong may have served as key nodes for subsequent domestic spread. These findings highlight the importance of integrated genomic surveillance for tracking dissemination and informing targeted infection control strategies.
Grass carp catalase inhibits GCRV replication through ROS scavenging-mediated immune suppression and autophagy.
Wang X, Zou X, Liu L … +9 more , Liang X, Wang H, Yang C, Li Y, Liao L, Zhu Z, Wang Y, Zhao J, He L
Virulence · 2026 Dec · PMID 42166546 · Full text
Catalase (CAT) is a key antioxidant enzyme that eliminates reactive oxygen species (ROS), thereby protecting organisms from oxidative stress and maintaining cellular homeostasis. In this study, we cloned and characterize...
Catalase (CAT) is a key antioxidant enzyme that eliminates reactive oxygen species (ROS), thereby protecting organisms from oxidative stress and maintaining cellular homeostasis. In this study, we cloned and characterized a CAT gene (CiCAT) from grass carp (), an important aquaculture species in China. The full-length cDNA of CiCAT is 2263 bp, with a 1575 bp open reading frame (ORF), and the encoded protein is highly conserved among fish species. CiCAT was constitutively expressed across all examined tissues, and its expression levels were significantly altered following infection with grass carp reovirus (GCRV) or stimulation with pathogen-associated molecular patterns (PAMPs). Subcellular localization analysis revealed that CiCAT was widely distributed in cells but co-localized with peroxisomes under HO treatment. Functionally, CiCAT enhanced resistance to HO and heavy metal stress, and it inhibited GCRV replication in fish cells. Mechanistic investigations demonstrated that CiCAT suppresses GCRV replication not through activation of the host antiviral immune response, but by scavenging ROS, which attenuates host immune signaling. This reduced immune activity in turn promotes autophagy via the mTORC1/ULK1 pathway, thereby restricting GCRV replication. Collectively, our findings provide novel insights into the antiviral role of CAT in teleost fish.
Pathogenicity and virulence of the blast fungus .
Molinari C, Talbot NJ
Virulence · 2026 Dec · PMID 42166451 · Full text
The blast fungus is the causal agent of the most serious disease of cultivated rice and an emerging threat to wheat production. Controlling blast diseases is therefore critical to ensuring global food security. In this...
The blast fungus is the causal agent of the most serious disease of cultivated rice and an emerging threat to wheat production. Controlling blast diseases is therefore critical to ensuring global food security. In this review, we describe the mechanism by which the fungus ruptures the plant cuticle to gain entry to host cells and the virulence determinants necessary for suppression of host immunity and rapid colonization of plant tissue.
Surveillance and biological characterization of H3 subtype avian influenza viruses in Eastern China.
Miao X, Zhao X, Zhang N … +8 more , Yin Y, Xu X, Wang J, Chen S, Wu H, Peng D, Qin T, Liu X
Virulence · 2026 Dec · PMID 42154626 · Full text
H3 subtype avian influenza viruses (AIVs) are frequently detected in poultry and wild birds, however, systematic characterization of contemporary isolates remains limited. We aimed to investigate the genetic evolution, p...
H3 subtype avian influenza viruses (AIVs) are frequently detected in poultry and wild birds, however, systematic characterization of contemporary isolates remains limited. We aimed to investigate the genetic evolution, pathogenicity, and transmission characteristics of H3 subtype AIVs circulating in Eastern China. Seven H3 subtype AIVs isolated between 2014 and 2021, including five H3N2, one H3N3, and one H3N6 strain, were analyzed. Phylogenetic analysis showed that all isolates belonged to the Eurasian lineage. Evidence of extensive reassortment with other AIV subtypes, as well as adaptive mutations associated with pathogenicity, and cross-species transmission, particularly in H3N2 subtype AIVs, was identified. Notably, H3N2 subtype AIVs exhibited dual receptor-binding properties, recognizing both SA α-2,3-Gal and SA α-2,6-Gal receptors. Although all isolates demonstrated low pathogenicity in chickens, mice, and guinea pigs, variations in transmission efficiency were observed. The H3N2 strain A/Duck/Anhui/LY/2021 showed the highest capacity for cross-species and aerosol transmission among guinea pigs. Overall, these findings indicate that H3 subtype AIVs have the potential for cross-species transmission and highlight the importance of continued surveillance of H3 subtype AIVs circulating in nature.
Immunological fitness of echinocandin-resistant (former ): The impact on the management of candidemia.
Basmaciyan L, Alvarez-Rueda N, Aldebert D … +9 more , Sahnouni H, Garnaud C, Patarot D, Ducreux A, Bon F, Winckler P, Le Pape P, Cornet M, Dalle F
Virulence · 2026 Dec · PMID 42154615 · Full text
(formerly ) () is a commensal yeast that is increasingly associated with invasive candidiasis. The rapid acquisition of echinocandin resistance by has raised public health concerns and led the WHO to classify it as a hi...
(formerly ) () is a commensal yeast that is increasingly associated with invasive candidiasis. The rapid acquisition of echinocandin resistance by has raised public health concerns and led the WHO to classify it as a high-priority fungal pathogen in 2022. However, the impact of antifungal resistance on the host immune response remains poorly understood. Since echinocandin resistance often involves alterations to the fungal cell wall, which is critical for host immune recognition, such mutations may affect fungal fitness and immune evasion. We analyzed the immunological fitness of echinocandin-resistant , defined here as their capacity to modulate innate immune recognition, phagocytosis, and survival, using clinical isolates from a patient with recurrent bloodstream infections. yeast-macrophage and yeast-human leukocyte co-culture models were used to evaluate immune responses. Echinocandin-resistant isolates exhibited modified cell wall composition. Compared to susceptible strains, the resistant isolates induced altered kinetics of pro-inflammatory cytokine responses, predominantly involving TNF-α and demonstrated sustained survival within leukocyte aggregates . These results suggest that resistance-associated cell wall remodeling can influence host-pathogen interactions. These findings suggest that altered immune interactions and delayed clearance may confer additional fitness advantages to echinocandin-resistant , potentially impacting the pathophysiological interactions between host and pathogen.
Phylogenomic framework and virulence gene boundaries of emerging Shiga toxin-producing O118 informed by the comprehensive profiling of 359 O118 genomes.
Rivera I, Koenig SSK, Rodriguez AL … +2 more , Bosilevac JM, Eppinger M
Virulence · 2026 Dec · PMID 42138049 · Full text
Non-O157 Shiga toxin-producing (STEC), particularly the O118 serogroup, are emerging pathogens linked to severe foodborne illnesses, which are characterized by the production of a potent phage-borne cytotoxin. This stud...
Non-O157 Shiga toxin-producing (STEC), particularly the O118 serogroup, are emerging pathogens linked to severe foodborne illnesses, which are characterized by the production of a potent phage-borne cytotoxin. This study explores the genomic landscape, virulence factors, and resistance traits of O118 STEC. We analyzed 357 publicly available O118 genomes, all but three available only in draft stage spanning ten different H-antigen types. To enhance the availability of high-quality reference genomes, we additionally included two O118:H16 STEC strains from our collection that were sequenced to closure. Multilocus sequence typing based on the 4,160 shared genes revealed phylogenetic clustering by H-type and delineated distinct STEC-phylogroups, alongside relationships to non-STEC pathovars such as uropathogenic (UPEC), enteropathogenic (EPEC), and enterotoxigenic (ETEC). Identified STEC-phylogroups encompass H6, H12, H16, and H2 strains with diverse Shiga toxin profiles (, , , , ). A subset of H2-STEC lacked , suggesting potential secondary phage loss. Most STEC groups carried the locus of enterocyte effacement (LEE). Further, a strong correlation was observed between H-antigens and subtypes, with specific pairings such as H6/, H16/, and H2/. Horizontally acquired pathogenicity islands, including O-island 122 in H16 strains and a novel pathogenicity-associated island carrying antibiotic resistance, along with other loci related to colonization and interbacterial competition, further enhance their virulence potential. Our findings underscore the genetic diversity and virulence potential of O118 STEC. Understanding such phylogroup-linked virulence and resistance traits is crucial for effective surveillance and public health interventions.
Single-cell spatial immune landscape of ASFV-infected porcine lung microenvironment.
Guo H, Cai H, Chen Y … +7 more , Zou Z, Yin S, Xu Y, Peng G, Jin M, Cao G, Dai J
Virulence · 2026 Dec · PMID 42135932 · Full text
African swine fever virus (ASFV) infection leads to severe lung lesions in the host, yet detailed insights into the immune response of the lung microenvironment to ASFV infection at the single-cell level remain limited....
African swine fever virus (ASFV) infection leads to severe lung lesions in the host, yet detailed insights into the immune response of the lung microenvironment to ASFV infection at the single-cell level remain limited. Here, we mapped the spatial immune landscape of the porcine lung microenvironment upon ASFV infection at single-cell resolution using an multi-gene mRNA co-detection method. We delineated the transcriptional dynamics of candidate genes in different immune cell types within the pig lungs upon ASFV infection. Additionally, we observed the dynamic changes in the number and spatial distribution of specific immune cell types in the lung microenvironment during ASFV infection. Moreover, the expression correlation between viral multi-gene family genes and host genes related to antiviral responses and apoptosis was identified. Our findings highlight the impact of viral genes on the host lung microenvironment and the complex viral-host interactions, providing insights into ASFV immune responses in porcine lungs at an level.
Integrated transcriptomic, molecular docking, and mendelian randomization analysis reveal a microbial-propionate-JUN pathway in renal ischemia-reperfusion injury.
Li J, Huang R, Wang X … +4 more , Zhang Y, Xu Z, Zhang P, Hu H
Virulence · 2026 Dec · PMID 42133662 · Full text
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and is characterized by oxidative stress, immune cell infiltration, and inflammatory signaling activation. Although gut microbiota and their...
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and is characterized by oxidative stress, immune cell infiltration, and inflammatory signaling activation. Although gut microbiota and their metabolites, especially short-chain fatty acids, are involved in systemic immune regulation, their role in renal IRI remains unclear. Here, we integrated transcriptomic analysis, gut-derived metabolite target prediction, molecular docking, and Mendelian randomization (MR) to explore potential microbiota-metabolite-host regulatory mechanisms in renal IRI. We identified 32 target genes of gut-derived metabolites using the gutMGene, Similarity Ensemble Approach, and SwissTargetPrediction databases. In two renal IRI datasets (GSE126805 and GSE90861), 263 and 641 differentially expressed genes were identified, respectively, and hub genes were mainly enriched in the TNF and IL-17 signaling pathways. Among them, JUN was identified as a key hub linking gut microbiota-associated metabolites to renal inflammatory signaling. MR analysis showed that was positively associated with kidney injury susceptibility [ = 0.026, odds ratio (OR) = 1.219], whereas was negatively associated with kidney injury susceptibility ( = 0.011, OR = 0.740). Because propionate, rather than butyrate, was the shared metabolite associated with both taxa, subsequent analyses focused on the propionate-JUN interaction. Molecular docking and dynamics supported strong binding between propionate and JUN. Overall, these findings suggest a potential gut-kidney regulatory axis involving -propionate-JUN-TNF/IL-17 signaling in renal IRI, providing new insight into microbiota-associated mechanisms of renal inflammatory injury.
Multicenter retrospective observational study on the clinical effectiveness of butyrate-producing containing probiotics in patients with COVID-19.
Morikawa Y, Kato H, Umemura T … +6 more , Hirai J, Shibata Y, Hagihara M, Asai N, Mikamo H, Iwamoto T
Virulence · 2026 Dec · PMID 42127027 · Full text
Butyrate-producing bacteria, which are components of the gut microbiome, activate host defense mechanisms against several types of infections, including respiratory viral infections. However, the clinical effectiveness o...
Butyrate-producing bacteria, which are components of the gut microbiome, activate host defense mechanisms against several types of infections, including respiratory viral infections. However, the clinical effectiveness of butyrate-producing (CB)-containing probiotics in patients with coronavirus disease 2019 (COVID-19) remains unclear. We investigated the in-hospital mortality, period of mechanical ventilation, and incidence of secondary bacterial pneumonia in patients with COVID-19 from 2020 to 2021. The patients were divided into the probiotic (27) and non-probiotic (256) groups. The two groups did not show a significant difference in the SOFA scores (probiotic vs. non-probiotic, 2.1 ± 2.3 vs. 2.1 ± 2.9). Additionally, all patients received antiviral agents to treat COVID-19; however, the two groups did not show significant difference in their distribution. However, patients receiving CB preparations showed the shorter periods of mechanical ventilation (1.1 ± 2.5 days vs. 3.9 ± 9.4 days). Although not statistically significant, they also showed lower incidence of secondary bacterial pneumonia (7.4% vs. 15.6%) and the lower in-hospital mortality (3.7% vs. 15.2%) compared to the non-probiotic group. This retrospective clinical study revealed that the administrations of CB preparations might attenuate clinical symptoms related to COVID-19 and improve mortality. However, further clinical and basic studies are required to validate our findings.
RecC is associated with divergent evolutions of clonal group 258 .
Hu D, Ye X, Wang J … +10 more , Mi S, Sun J, Dai P, Huang T, Zhang J, Luo X, Ma Q, Jiang X, Wu S, Zhang H
Virulence · 2026 Dec · PMID 42127018 · Full text
Clonal group 258 strains are notorious but their divergent evolutions were identified through analysis of 80 sequence type (ST) 258, 284 ST11, and 15 ST512 genomes. The serotypes of ST11 strains differed from those of S...
Clonal group 258 strains are notorious but their divergent evolutions were identified through analysis of 80 sequence type (ST) 258, 284 ST11, and 15 ST512 genomes. The serotypes of ST11 strains differed from those of ST258 and ST512. Genes and dominated carbapenem-resistance in ST258 strains, whereas they were found in ST11 and ST512, respectively. The carbapenem-resistance rates were 93.75%, 86.97%, and 100.0% among the ST258, ST11, and ST512 strains, respectively while the hypervirulence and carbapenem-resistance rates were 2.50%, 35.92%, and 0.00%, respectively. The wide carbapenem-resistance and the hypervirulence were determined by drug-resistance and virulence plasmids respectively. Except , , and , was significantly different: RecC for the three groups and RecC for ST11; RecC ST11 strains presented a higher rate of hypervirulence plus carbapenem-resistance than those carrying RecC. RecC and RecC presented the difference of an amino acid side chain, leading to the disappearance of the hydrogen bond. Single-Nucleotide Polymorphism analysis verified closer relationship between ST258 and ST512 than ST11. RecC facilitated pK2044 to HS11286 (5.61 times) while deletion exerted advantages on pKPHS2 to NTUH-K2044 (5.49 times). The retention rates of pK2044 in HS11286+ kept over 80.0% in the 8 passages while those in HS11286+ declined to less than 3.0% in the last 5 passages. In conclusion, different from ST258 and ST512, ST11 strains show an overwhelming propensity to become hypervirulent and carbapenem-resistant. RecC mutation facilitates the transfer of virulence plasmids into carbapenem-resistant strains but decreases their retention in the strains.
Clinical and genomic profiling of in liver abscesses.
Aurnhammer F, Baltzer MM, Butt J … +10 more , Marr LS, Rath A, Kieninger B, Schneider-Brachert W, Utpatel C, Niemann S, Steinmann E, Dechêne A, Steinmann J, Neumann B
Virulence · 2026 Dec · PMID 42118687 · Full text
() is an opportunistic Gram-negative pathogen responsible for a variety of infections, including liver abscesses (LA). These are associated with hypervirulent (hvKp). This study aimed to characterize the clinical and mo...
() is an opportunistic Gram-negative pathogen responsible for a variety of infections, including liver abscesses (LA). These are associated with hypervirulent (hvKp). This study aimed to characterize the clinical and molecular features of from patients with LA at a German tertiary care hospital over a 2-y period (2022-2023). Among 111 recorded LA, was detected in 27% ( = 30) of cases. Of these, 12 patients had monomicrobial LA. Clinical metadata, including patient demographics, underlying diseases, and microbiological findings, were analyzed and correlated with genomic data to explore associations between genetic traits and clinical presentations. We identified seven cases of hypervirulent liver abscesses (hvKpLA) and five cases of non-hypervirulent liver abscesses (KpLA). The study found that hvKp was most commonly associated with specific sequence types (ST23-KL1, ST86-KL2) and hypervirulence-associated plasmids. Phylogenetic analysis revealed high genetic diversity, with no evidence of nosocomial transmission. Notably, diabetes mellitus (DM) was observed for five cases and may represent a risk factor for severe infections. In conclusion, monomicrobial LA infections were caused by hypervirulent strains in 58% of cases. Further, an hvKp case prevalence of 6.3% was estimated among all recorded liver abscesses. These findings contribute to a better understanding of the molecular epidemiology of hvKp and emphasize the importance of integrating clinical and genomic data for more accurate risk stratification and surveillance.
Identification of DksA as a novel pro-inflammatory mediator of under conditions mimicking chronic cystic fibrosis lung infection.
Wauters M, Bollé L, De Meester G … +11 more , Van den Bossche S, Grassi L, Van Haver D, Dufour S, Devos S, Impens F, Van Braeckel E, Hirsch AKH, Whiteley M, Saelens X, Crabbé A
Virulence · 2026 Dec · PMID 42117785 · Full text
Chronic infection with is a major driver of airway inflammation, which plays a central role in the progression of cystic fibrosis (CF) lung disease. During long-term colonization, adapts to the CF lung by downregulatin...
Chronic infection with is a major driver of airway inflammation, which plays a central role in the progression of cystic fibrosis (CF) lung disease. During long-term colonization, adapts to the CF lung by downregulating virulence factors and adopting a biofilm-associated, mucoid lifestyle. Despite the expected reduction in immune activation due to these adaptations, excessive inflammation persists, a paradox that remains poorly understood. Our objective was to identify novel bacterial mediators sustaining persistent inflammation by in the CF lung. To this end, we analyzed clinical CF isolates, cultured them in synthetic CF sputum medium, and exposed 3D lung epithelial cell cultures to the resulting cell-free supernatants. There was considerable variability in pro-inflammatory activity among the isolates, with a subset of the isolates inducing strong IL-8 secretion by the 3D cells despite low production of known virulence factors. Comparative proteomics analysis of the cell-free supernatants of pro-inflammatory and immunosuppressive isolates revealed several mediators not previously linked to inflammation. Thirteen of these candidate pro-inflammatory mediators were selected for further analysis. Using transposon mutants lacking the respective mediators, DksA (a transcription factor) was confirmed as an immunomodulatory mediator in the 3D lung model. Finally, analysis of existing transcriptomes of in CF sputum revealed that was found to be one of the most strongly expressed genes in this patient population, highlighting the relevance of our findings. In conclusion, we identified a novel mediator that may contribute to CF airway inflammation.
Integrated transcriptomic and proteomic analysis reveals inflammatory activation and blood-brain barrier disruption during meningitis-associated extraintestinal pathogenic infection.
Li Z, Chen M, Du Y … +6 more , Jia K, Lu Y, Yu X, Cao X, Peng L, Fang R
Virulence · 2026 Dec · PMID 42115138 · Full text
Meningitis-associated extraintestinal pathogenic (ExPEC) is a major cause of bacterial meningitis, yet the molecular mechanisms underlying blood-brain barrier (BBB) disruption during infection remain unclear. We employe...
Meningitis-associated extraintestinal pathogenic (ExPEC) is a major cause of bacterial meningitis, yet the molecular mechanisms underlying blood-brain barrier (BBB) disruption during infection remain unclear. We employed integrated transcriptomic and proteomic analysis to investigate host responses of human cerebral microvascular endothelial cell line hCMEC/D3 to ExPEC strain RS218 infection. Multi-omics integration revealed coordinated immune activation, with upregulation of innate immune signaling pathways such as Toll-like receptor, NOD-like receptor, TNF, and IL-1 signaling, as well as antigen presentation pathways. In addition, we identified direct molecular evidence for BBB compromise, including concordant downregulation of tight junction protein ZO-1 at both transcriptomic and proteomic levels, validated by immunofluorescence showing reduced ZO-1 expression in infected cells. Several processes that may contribute to BBB breakdown were identified, such as glycosaminoglycan degradation, cytoskeletal reorganization, and suppression of TGF-β/SMAD signaling. Moreover, extensive metabolic dysregulation was evident, including downregulation of neural metabolic support functions and compromised protein homeostasis. Abundant discordance between transcriptomic and proteomic levels revealed complex post-transcriptional control mechanisms. experiments demonstrated RS218-induced cell death in brain endothelial cells, microglial cells, and peritoneal macrophages. Animal experiments confirmed systemic metabolic disruption, immune cell alteration, functional BBB disruption, and profound brain cytokine elevation. This integrated analysis advances our understanding of bacterial meningitis pathogenesis and identifies potential therapeutic targets.
Microbiota and head and neck cancers: Mechanistic insights and translational potential.
Cui X, Zhang X, Li X … +6 more , Ma Y, Hu J, Li Z, Yang Y, Ma Z, Liu Y
Virulence · 2026 Dec · PMID 42113945 · Full text
Head and neck cancers (HNCs) impose a substantial global health burden, particularly in Asia and China. Emerging evidence highlights the pivotal role of oral, pharyngeal, and intratumoral microbiota in HNC pathogenesis....
Head and neck cancers (HNCs) impose a substantial global health burden, particularly in Asia and China. Emerging evidence highlights the pivotal role of oral, pharyngeal, and intratumoral microbiota in HNC pathogenesis. Microbial dysbiosis promotes tumor initiation and progression through interconnected mechanisms, including chronic inflammation, immune modulation, and metabolic reprogramming. Specifically, dysbiosis induces a pro-tumorigenic microenvironment by triggering persistent inflammation, disrupting immune surveillance, and generating oncogenic metabolites or depleting protective compounds. Comparative analyses reveal both shared and site-specific microbial signatures, reflecting complex host - microbe interactions. Notably, the microbiota holds promise as a source of noninvasive biomarkers for early detection and prognosis, and may influence responses to immunotherapy and chemoradiotherapy. However, challenges remain in methodological standardization and in establishing causal relationships. Integrating multi-omics approaches with functional studies will be essential to advance precision diagnostics and microbiota-targeted strategies for personalized HNC management.
Genomic insights into multidrug-resistant bacteria: Emergence of in , in and from clinical settings.
Hameed MF, Shoaib M, Peng K … +2 more , Wang Z, Li R
Virulence · 2026 Dec · PMID 42102272 · Full text
This study presents a comprehensive genomic analysis of multidrug-resistant (MDR) clinical isolates from Anhui Province, China, focusing on , , and . The strain EC385 belong to ST1011 and rST1640 harbors multiple resist...
This study presents a comprehensive genomic analysis of multidrug-resistant (MDR) clinical isolates from Anhui Province, China, focusing on , , and . The strain EC385 belong to ST1011 and rST1640 harbors multiple resistance and virulence determinants and five plasmids, including IncI2 and IncHI2, with a co-occurrence of with , , , , and . Among isolates, KP304 (ST15/rST19202) and KP297 (ST15/rST19202) were carrying IncFII(pBK30683) and IncFIB plasmids, while KP69 (ST11/rST31218) harbored five plasmids, including IncHI1B and IncR. Notably, KP304, KP297, and KP69 exhibited MDR due to acquisition of along with other multiple resistance determinants including , (A), , , (KP304 and KP297), and (KP69). In the current finding, is reported to carry , alongside IncFII(pBK30683) and IncR plasmids. These findings highlight the genomic diversity and alarming spread of resistance mechanisms in clinical pathogens, emphasizing the urgent need for surveillance to combat the antimicrobial resistance.
Comparative analysis of viral biological characteristics and pathogenicity of representative prevalent avian reovirus strains from genotypes I to V.
Meng F, Li R, Zhang D … +9 more , Zhou H, Zhou C, Wang N, Wang Y, Guo F, Ding L, Lang F, Yang L, Cheng Z
Virulence · 2026 Dec · PMID 42100896 · Full text
The variable pathogenicity of avian reovirus (ARV), driven by genotypic diversity, poses significant control challenges to the global poultry industry. However, biological and pathogenic distinctions among genotypes rema...
The variable pathogenicity of avian reovirus (ARV), driven by genotypic diversity, poses significant control challenges to the global poultry industry. However, biological and pathogenic distinctions among genotypes remain poorly characterized. We performed a comprehensive comparison of 14 ARV strains (genotypes I-V), evaluating viral biological characteristics and pathogenicity indicators. Phylogenetic analysis of these isolates and field strains in China based on the σC gene revealed co-circulation of multiple genotypes (predominantly I and II), with epidemic strains actively evolving and genetically distant from the S1133 vaccine. Structural analysis localized conformational B-cell epitopes of σC protein primarily to the C-terminal globular head and neck, with a highly conserved core antigenic scaffold formed by key residues, while peripheral residues showed genotype-specific variation. Recombination analysis suggests that genotype V (SDAU-G5-DG) likely emerged through recombination with genotype VI. Genotypes I (SDAU-G1-AN4) and IV (SDAU-G4-m4) exhibited enhanced replication and lethality in cell culture and chicken embryos. In vivo, all strains caused growth retardation, lameness, tenosynovitis, and immune organ atrophy, but the tested genotypes I and IV were most virulent. Distinct tissue tropisms were observed: genotypes I and V induced cardiac and hepatic lesions, whereas genotypes I and III caused intestinal damage. Immunologically, genotypes I and IV triggered strong early pro-inflammatory cytokine responses and significantly upregulated MMP13 and Wnt14 at 7 dpi. This points to severe immune activation and a high risk of joint injury. These distinct biological and pathogenic profiles among the tested ARV strains underscore the need for genotype-specific vaccine strategies.
Neutralizing epitope mapping for deltacoronavirus receptor-binding domain and seroepidemiological survey across different animal species.
Li D, Hao L, Huang B … +9 more , Wang Z, Wang Z, Guo M, Zhang Y, Deng J, Li Y, Zhao S, Tian K, Li X
Virulence · 2026 Dec · PMID 42093621 · Full text
Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that poses a significant threat to the global swine industry and carries a potential public health risk. The development of neutralizing monoclonal antibod...
Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that poses a significant threat to the global swine industry and carries a potential public health risk. The development of neutralizing monoclonal antibodies (mAbs) is crucial for preventing and controlling PDCoV. However, research on neutralizing linear epitopes within the PDCoV receptor-binding domain (RBD) and the establishment of serological assays based on such mAbs remains limited. In this study, we generated two neutralizing mAbs, 1C12 and 3A11, targeting the PDCoV RBD. Epitope mapping revealed that 1C12 recognizes a linear epitope (DFGEARLD), whereas 3A11 binds to a conformational epitope. Further residue analysis identified Arg321 as the most critical residue for binding to 1C12. Additionally, the integrity of the entire RLD motif was found to be indispensable for the conformational recognition by mAb 3A11. Using these mAbs, we developed two blocking enzyme-linked immunosorbent assay (bELISA) methods (bELISA-1C12 and bELISA-3A11). Evaluation of 150 clinical samples demonstrated that bELISA-1C12 exhibited 93.3% concordance with a virus neutralization test (VNT), indicating higher diagnostic sensitivity than bELISA-3A11 (92.7%). A large-scale serosurvey of pig populations across ten Chinese provinces in 2025, conducted using bELISA-1C12, revealed a PDCoV seropositivity rate of 13.6%. Notably, when extending the serological screening to 21 additional animal species, we detected PDCoV antibodies in peafowl serum for the first time, suggesting possible exposure to the virus. This study identifies key antigenic epitopes on the PDCoV RBD and provides valuable tools for epidemiological surveillance and assessing the transmission risk of PDCoV.
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