Virulence最新文献

{"title":"Enterovirus 2B protein: From viroporin to membrane stress sensor, mechanistic principles of multi-pathway regulation.","authors":"Zengjun Ji, Yikun Chen, Hongxing Shen","doi":"10.1080/21505594.2026.2739074","DOIUrl":"10.1080/21505594.2026.2739074","url":null,"abstract":"<p><p>Enterovirus 2B is a highly conserved, functionally versatile, nonstructural protein. The classic viroporin model, which restricts its role to ion channel formation, cannot account for its interactions with host factors such as Bcl-2-associated X protein, interleukin enhancer-binding factor 2, and karyopherin subunit alpha 1, nor its functional divergence among enteroviruses. We propose a novel, testable membrane stress sensor hypothesis: the transmembrane helices of 2B sense lipid composition and pH changes, and through conformational dynamics, spatiotemporally coordinate calcium signaling, cell death pathway selection, including apoptosis, pyroptosis, autophagy, and ferroptosis, and immune evasion. We elaborate on this framework across six dimensions: structure-function mapping, calcium signaling, cell death pathways, immune evasion, evolutionary footprint, and antiviral targeting, along with cross-virus comparisons. We highlight key evidence gaps and limitations, and propose several future research directions. This framework establishes a mechanistic foundation for understanding 2B function and guiding rational anti-enteroviral drug designs.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"18 1","pages":"2739074"},"PeriodicalIF":6.8,"publicationDate":"2027-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolic characteristics in PWHIV with metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"Huiting Liu, Tianzhen Xu, Yongzheng Guo, Xiaotang Zhou, Chunhui Yan, Biao Zhu, Yirui Xie","doi":"10.1080/21505594.2026.2739091","DOIUrl":"10.1080/21505594.2026.2739091","url":null,"abstract":"<p><p>The global prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among persons with HIV (PWHIV) is estimated at 34%. This study examined the influence of gut microbial and metabolic alterations in PWHIV with MASLD. We conducted 16S rRNA sequencing on 60 fecal samples (24 from HIV group and 36 from HIV-MASLD group) to assess microbial composition, and employed LC/MS-based metabolomics on both fecal and plasma samples to identify variations in metabolites. An exploratory analysis was performed to compare plasma cytokines and oxidative stress markers between the two groups. Sequencing in the HIV-MASLD group showed lower <i>Faecalibacterium</i> and <i>Anaerobutyricum</i>, and higher <i>Klebsiella</i>, <i>Escherichia</i>, and <i>Enterococcus</i>. Metabolomic analysis revealed a reduction in anti-inflammatory metabolites (Dodecanedioic acid, 5-Phenylvaleric acid, Kynurenic acid) and antioxidant metabolites, coupled with an increase in the pro-inflammatory metabolite Gamma-Glutamyl-L-Putrescine in the HIV-MASLD group. And plasma analysis indicated a decline in 20-carboxy arachidonic acid. Additionally, <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> correlated positively with anti-inflammatory metabolites, while <i>Klebsiella</i>, <i>Enterobacter</i>, and <i>Citrobacter</i> correlated negatively. Furthermore, <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> also showed a moderate negative correlation with MDA levels. A random forest model using plasma metabolites showed the optimal discriminative ability for HIV-MASLD (AUC = 0.819 ± 0.0059). Differences in gut microbiota and metabolites in PWHIV may affect MASLD progression by influencing inflammation and oxidative stress. Modulating gut microbiota, such as adding <i>Faecalibacterium</i> and <i>Anaerobutyricum</i>, could be a treatment strategy for HIV-MASLD. Plasma metabolites have potential as noninvasive markers.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"18 1","pages":"2739091"},"PeriodicalIF":6.8,"publicationDate":"2027-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutralizing epitope mapping for deltacoronavirus receptor-binding domain and seroepidemiological survey across different animal species.","authors":"Dexin Li, Liying Hao, Baicheng Huang, Zhiyan Wang, Zenglin Wang, Menghao Guo, Yunjing Zhang, Junhua Deng, Yufang Li, Shaoruo Zhao, Kegong Tian, Xiangdong Li","doi":"10.1080/21505594.2026.2668161","DOIUrl":"10.1080/21505594.2026.2668161","url":null,"abstract":"<p><p>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 (³¹⁶DFGEARLD³²³), 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 ³²¹RLD³²³ 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.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"17 1","pages":"2668161"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Hematodinium</i> sp. infection alters hemolymph bacteriome composition and function in shore crabs, <i>Carcinus maenas</i>.","authors":"Jessica E Thomas, Miguel Lurgi, Charlotte E Davies, Andrew F Rowley, Christopher J Coates","doi":"10.1080/21505594.2026.2709259","DOIUrl":"10.1080/21505594.2026.2709259","url":null,"abstract":"<p><p><i>Hematodinium</i> sp. is a parasitic dinoflagellate that infects and causes disease in a large fraction of decapod crustaceans in the Northern Hemisphere. The shore crab <i>Carcinus maenas</i> is susceptible to this parasite in its native range of European coastlines and along its invasive fronts. The parasite enters the host from the surrounding water, and fueled by the hemolymph (blood) resources, proliferates until host tissues are overrun. To improve our knowledge of the shore crab-<i>Hematodinium</i> pathosystem, we profiled the hemolymph microbiome of control and <i>Hematodinium</i>-positive crabs with low (early clinical) and high (late clinical) parasite levels through bacterial 16S rRNA V3-V4 meta-barcoding (<i>n</i> = 64). Concurrently, we assessed hemolymph condition through quantification of circulating hemocytes (immune cells) and bacterial colony forming units. Progression of <i>Hematodinium</i> sp. infection coincided with gradual changes in bacterial community composition. These changes were driven by shifts in relative abundances of specific taxa, e.g. <i>Corynebacterium, Flavobacterium</i>. Furthermore, alterations in bacterial communities were accompanied by marked shifts in metabolic signatures from stress and virulence dominated (including biofilm formation) to catabolism, peptide transport, and tissue putrefaction at the terminal stage of parasitemia. We present the first account of microbiome dynamics in healthy shore crabs and those overcome by <i>Hematodinium</i> sp. Our experiments reveal a clear link between bacterial community structure-function and the advancing disease state.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2709259"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning prediction of functional cure to pegylated interferon-alpha therapy in two HBV populations: Advantaged populations and HBeAg-negative patients.","authors":"Jiajie Li, Huilin Li, Caorui Lin, Renquan Jiang, Longfei Wang, Yujue He, Xin Yang, Kaitao Gong, Zhen Xun, Qi Zheng","doi":"10.1080/21505594.2026.2629088","DOIUrl":"10.1080/21505594.2026.2629088","url":null,"abstract":"<p><p>Despite advances in antiviral therapy, the rate of functional cure for chronic hepatitis B (CHB) remains unsatisfactory, and developing an applicable prediction model is pivotal to improving it. Thus, we aimed to identify key predictive factors and develop prognostic models for functional cure in HBeAg-negative patients and the advantaged populations. This retrospective study included 202 HBeAg-negative CHB patients (114 classified as advantaged populations) receiving pegylated interferon-alpha (PEG-IFNα) therapy for model derivation and internal validation, and 183 HBeAg-negative CHB patients (117 classified as advantaged populations) for model external validation. Using 48 routinely collected clinical indicators, we constructed prediction models through LASSO regression followed by multivariable logistic regression. Two nomogram-based models were developed: the SHAN model, based on four independent predictors - ln (HBsAg +1), age, neutrophil percentage (NE%), and sex - was tailored for HBeAg-negative patients. For the advantaged populations, two additional variables - alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) - were incorporated into the FLASH-N model. Both models demonstrated strong discrimination, with AUCs of 0.908 in the training set and 0.949 in the test set for the SHAN model and an AUC of 0.920 (bootstrap-corrected to 0.889) for the FLASH-N model in the advantaged populations. In external validation, SHAN model achieved an AUC of 0.861, and FLASH-N achieved an AUC of 0.800. Calibration plots and decision curve analysis further confirmed the robustness, accuracy, and clinical utility of both nomograms. By leveraging routinely available baseline variables, these models offer powerful tools for predicting functional cure in CHB, enabling refined risk stratification and more personalized clinical decision-making.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2629088"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGFBP7 induces phenotypic shift from platelet-mediated autoagglutination to rosetting of <i>Plasmodium knowlesi</i>-infected erythrocytes.","authors":"Joo-Yie Chin, Laurent Rénia, Wenn-Chyau Lee","doi":"10.1080/21505594.2026.2711530","DOIUrl":"10.1080/21505594.2026.2711530","url":null,"abstract":"<p><p>Zoonotic malaria caused by <i>Plasmodium knowlesi</i> is an emerging infectious disease with persistent transmission in Southeast Asia over the past two decades. This zoonosis causes potentially life-threatening hematological complications such as thrombocytopenia. While mechanisms behind the malaria-induced acute thrombocytopenia remain to be fully deciphered, it is believed to be associated with the cytoadherence of <i>Plasmodium</i>-infected erythrocytes (IRBC) to platelets. Of note, platelet-mediated cytoadherence of IRBC gives rise to platelet-mediated clumping of IRBC, also known as IRBC autoagglutination. Nevertheless, most of the autoagglutination studies were performed with <i>P. falciparum</i>. In this study, we characterized autoagglutination of <i>P. knowlesi</i> and <i>P. falciparum</i>, and investigated the relationship between IRBC autoagglutination and rosetting rates (another IRBC cytoadherence phenomenon). Autoagglutination was found to be dependent on the presence of human serum and platelets, where the presence of platelets favored IRBC autoagglutination over rosetting. The autoagglutination of <i>P. knowlesi</i> and <i>P. falciparum</i> was mediated by CD36, where antibody blockade of CD36 inhibited autoagglutination and drove the IRBC to form more rosettes with the uninfected erythrocytes (URBC). Antibody blocking of P-selectin reduced only the autoagglutination of <i>P. falciparum</i> with no effect on the rosetting rates. Notably, the presence of IGFBP7 (a human-derived protein that facilitates the formation of type II rosettes) suppressed autoagglutination while stimulating rosetting rates of IRBC. Given the ability of IGFBP7 to alter the <i>Plasmodium</i>-mediated cytoadherence dynamics between autoagglutination and rosetting, this human protein may alter the pathobiology of malaria, hence the disease outcomes of the infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"17 1","pages":"2711530"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of isokurarinone as an ATCase-engaging lead with potent activity against methicillin-resistant <i>Staphylococcus aureus</i>.","authors":"Xinyuan Cao, Xiaorong Yang, Lixia Dai, Xueyan Liu, Zile Gong, Xiaoyan Yu, Yuchao Ma, Tong Bu, Haowen Wu, Xiaolou Miao, Xiaofei Shang, Changcai Bai","doi":"10.1080/21505594.2026.2707766","DOIUrl":"10.1080/21505594.2026.2707766","url":null,"abstract":"<p><p>The global proliferation of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) persists as a significant contributor to challenging infections, highlighting the urgent necessity for therapies that utilize novel mechanisms. Aspartate transcarbamoylase (ATCase), which catalyzes the initial committed step of <i>de novo</i> pyrimidine biosynthesis, represents a promising metabolic target with potential relevance to MRSA fitness and persistence. Through structure-based virtual screening and experimental validation, we identified the flavonoid isokurarinone as a compound targeting ATCase, demonstrating potent anti-MRSA activity. Docking and molecular dynamics simulations, along with surface plasmon resonance and differential scanning fluorimetry, provided evidence for direct binding, which was accompanied by a decrease in <i>pyrB</i> expression and a reduction in ATCase activity. Non-targeted metabolomics revealed a disruption of pyrimidine nucleotide homeostasis, coinciding with impaired membrane integrity, reduced proton motive force, decreased intracellular ATP levels, and increased oxidative stress. Isokurarinone also showed an additive interaction with vancomycin <i>in vitro</i>, inhibited biofilm formation and altered the expression of virulence-associated genes. Safety evaluation showed cell-type-dependent cytotoxicity in mammalian cells, while no obvious acute oral toxicity was observed in mice at a single dose of 2 g/kg. In a murine model of MRSA-infected wounds, isokurarinone accelerated wound closure, reduced bacterial burden, and attenuated local inflammatory mediators. Collectively, these findings support the notion of ATCase as a metabolism-guided target for MRSA and nominate isokurarinone as a promising lead scaffold for therapeutic development.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2707766"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial efficacy and mechanism of the novel antimicrobial peptide lachnospirin-1 against <i>Acinetobacter baumannii</i>.","authors":"Pengfei She, Mengna Li, Yiqing Liu, Guanqing Huang, Shaowei Guo, Dan Xiao, Yelan Hong, Lihua Lu, Yong Wu","doi":"10.1080/21505594.2026.2646808","DOIUrl":"10.1080/21505594.2026.2646808","url":null,"abstract":"<p><p>The treatment of carbapenem-resistant <i>A. baumannii</i> (CRAB) infections has become a major global medical challenge; therefore, there is an urgent need for new antimicrobial development. Antimicrobial peptides hold great promising potential due to their rapid bactericidal activity and low induction of drug resistance. In this study, we screened and synthesized the antimicrobial peptide lachnospirin-1, which exhibited significant bactericidal activity against CRAB and can also effectively eliminate its biofilms and persister cells. Mechanism studies, including fluorescent probe detection, transmission electron microscopy observations, and molecular dynamics simulations, et al. indicated that lachnospirin-1 exerts its effects through multiple mechanisms, such as disrupting bacterial cell membranes, neutralizing lipopolysaccharide, as well as inducing oxidative stress, which also demonstrates its certain potential. In addition, the favorable safety profile and effective <i>in vivo</i> bactericidal activity of lachnospirin-1 were determined by mouse models. Overall, our study found that lachnospirin-1 has considerable research potential as a lead compound and possesses latent value as a clinical therapy for refractory infections caused by CRAB.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2646808"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isotopic tracing in <i>Mycobacterium tuberculosis</i>-infected alveolar epithelial cells indicates metabolic specificity to their virulence and drug-resistance status.","authors":"Subia Akram, Shyam Kumar Masakapalli, Ranjan Kumar Nanda","doi":"10.1080/21505594.2026.2723630","DOIUrl":"10.1080/21505594.2026.2723630","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a global health threat aggravated by the emergence of drug-resistant strains. <i>Mycobacterium tuberculosis</i> promotes metabolic remodeling within host cells to support its survival. Type II alveolar epithelial cells have been established as a primary niche for bacterial infection, adherence, and invasion. However, compared to macrophages, metabolic interactions within these cells, particularly the strain-specific exploitation of host metabolism, remain inadequately explored. To address this, we integrated intracellular bacterial growth and host cell viability assays with C-based proteinogenic amino acid kinetics to gain insights into metabolic changes in A549 alveolar epithelial cells infected with laboratory strains (virulent H37Rv, avirulent H37Ra) and clinical isolates (drug-resistant S6 and S11; drug-sensitive S4 and S5). Virulent strain H37Rv showed higher intracellular growth (6-fold increase) but significantly reduced host cell viability relative to avirulent H37Ra. Interestingly, the multidrug-resistant isolate S6 showed the highest intracellular growth (18-fold increase) while maintaining host cell viability. Mass isotopomer distribution analysis revealed that virulent strains showed increased reliance on central carbon metabolism, including glycolysis, the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle. H37Rv showed greater ¹³C enrichment in host amino acids, such as alanine (1.6-fold), compared to H37Ra. Drug-resistant isolates displayed distinct ¹³C enrichment in TCA-derived threonine (0.21-0.25%), methionine (0.18-0.28%), and lysine (0.12-0.27%). We observed ¹³C enrichment in essential amino acids (lysine, methionine, threonine, valine) across all infected conditions, confirming the pathogen's dependence on host-derived metabolic intermediates. These findings highlight the need to explore host-to-pathogen amino acid transport as a precise host-directed therapeutic target.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"17 1","pages":"2723630"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic analyses identify nosocomial transmission of ST23 carbapenem-resistant hypervirulent <i>Klebsiella pneumoniae</i> mediated by a conjugative IncFII_K2 NDM-1 plasmid.","authors":"Tao Chen, Xueting Wang, Luying Xiong, Yan Geng, Hui Ding, Yunbo Chen, Ping Shen, Yonghong Xiao","doi":"10.1080/21505594.2026.2668167","DOIUrl":"10.1080/21505594.2026.2668167","url":null,"abstract":"<p><p>The World Health Organization has identified ST23 carbapenem-resistant hypervirulent <i>Klebsiella pneumoniae</i> (CR-hvKP) as a critical public health threat. Through China's national surveillance system (BRICS), we identified and characterized ST23 CR-hvKP bloodstream isolates from 2019-2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected across two hospitals, including a nosocomial transmission pair (differing by only 2 core SNPs). Clinical outcomes revealed that three of the four patients achieved recovery following appropriate antibiotic therapy, with one mortality case attributed to underlying comorbidities. All four ST23 isolates demonstrated resistance to multiple antibiotics, indicating a pattern of multidrug resistance. Genomic analysis uncovered diverse resistance mechanisms: the nosocomial transmission pair possessed conjugative IncFII_K2 NDM-1 plasmids, while the others harbored conjugative IncFII_K34 KPC-2 plasmids, which exhibited reduced carbapenem resistance attributed to the downregulation of <i>bla</i>_KPC-2 expression. Conjugation assays revealed high transferability (10^-5 for IncFII_K2 NDM-1; 10^-4 for IncFII_K34 KPC-2). Whole-plasmid comparative genomics analysis suggested that the IncFII_K2 NDM-1 plasmids shared > 99% identity with historical IncFII_K2 plasmid backbones from Chinese <i>K. pneumoniae</i> isolates (2014-2022), suggesting local evolution. Notably, only 4.4% (26/590) of global IncFII_K2 plasmids carried <i>bla</i>_NDM-1 and all IncFII_K2 NDM-1 plasmids maintain conjugative potential. All strains harbored conserved virulence plasmids and maintained hypervirulence, as indicated by a mouse infection model, with the exception of one strain that exhibited <i>cps</i> mutations. This study reports the first genomic evidence of a high-frequency conjugative IncFII_K2 NDM-1 plasmid in a hospital-transmitted ST23 CR-hvKP clone, highlighting the need for plasmid-focused surveillance to control this potential threat.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"17 1","pages":"2668167"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}