Emerging Microbes & Infections最新文献

{"title":"<i>Streptococcus suis</i> Stk1 sensitizes epithelial cells to ferroptosis and exacerbates disruption of the respiratory epithelial barrier.","authors":"Lang Tian, Ruicheng Yang, Ting Qi, Wenquan Ouyang, Hongshuo Liu, Dong Huo, Hang Li, Chuyue Zhou, Manman Xu, Haojie Li, Qingyun Liu, Dang Wang, Chen Tan, Huanchun Chen, Xiangru Wang","doi":"10.1080/22221751.2026.2627066","DOIUrl":"10.1080/22221751.2026.2627066","url":null,"abstract":"<p><p><i>Streptococcus suis</i> serotype 2 (SS2), a significant zoonotic pathogen, initiates systemic infection by breaching the respiratory epithelial barrier. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly implicated in the pathogenesis of various infectious diseases, yet its role in SS2-induced epithelial barrier dysfunction remains unknown. Here, we demonstrate SS2 infection sensitizes airway epithelial cells to ferroptosis, leading to the accumulation of lipid peroxides, upregulation of the transcriptional repressor Snail1, and subsequent downregulation of intercellular junction proteins. This cascade compromises epithelial integrity and promotes bacterial translocation. Mechanistically, we found SS2 overwhelms the cellular redox defense system and identified bacterial eukaryotic-like serine/threonine kinase 1 (Stk1) as the key mediator of this process. Stk1 directly interacts with host protein Keap1, which stabilizes the Keap1-Nrf2 complex. This stabilization enhances the ubiquitination and subsequent proteasomal degradation of Nrf2, the master regulator of antioxidant response, thereby crippling cell's ability to neutralize lipid peroxides. In summary, this study unveils a novel virulence mechanism wherein SS2 effector Stk1 promotes Nrf2 degradation to trigger ferroptosis, ultimately leading to the disruption of respiratory epithelial barrier. These findings suggest that inhibiting ferroptosis could represent a promising therapeutic strategy for clinical prevention and treatment of SS2 infections.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2627066"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can we escape from top-priority ESKAPE pathogens?","authors":"Lingbing Zeng, Youjun Feng, Minggui Wang","doi":"10.1080/22221751.2026.2614739","DOIUrl":"10.1080/22221751.2026.2614739","url":null,"abstract":"<p><p><b>ABSTRACT</b>The ESKAPE pathogens - <i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, and <i>Enterobacter spp.</i> - are designated by the World Health Organization as critical-priority multidrug-resistant organisms. These bacteria are leading contributors to the global antimicrobial resistance crisis, significantly increasing morbidity, mortality, and healthcare costs worldwide. Their capacity to evade conventional antibiotics continues to complicate clinical management and undermine infection control efforts. Tackling the global threat of ESKAPE pathogens demands coordinated and sustained interventions. This mini review summarizes recent evidence on the burden and prevalence of ESKAPE infections and assesses emerging strategies to combat resistance. Progress in surveillance and promising preclinical and clinical studies of novel therapies underscore that integrated approaches are crucial. Moving forward, a balanced emphasis on prevention, surveillance, and therapeutic innovation will be essential to mitigating the threat posed by ESKAPE pathogens over the coming decade.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2614739"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emergence and biological characteristics of linezolid-resistant <i>Clostridioides difficile</i> isolates in the Asia-Pacific region.","authors":"Yu Chen, Xinwei Chen, Hangcong Xu, Heng Shen, Xing Liu, Fen Wan, Yuning Han, Xiaojun Song, Jun Li, Hong Du, Xingli Fan, Yan Wu, Yun Luo, Dazhi Jin","doi":"10.1080/22221751.2026.2627070","DOIUrl":"10.1080/22221751.2026.2627070","url":null,"abstract":"<p><p>Linezolid-resistant <i>Clostridioides difficile,</i> conferred by the acquisition of <i>cfr</i>-like genes, has been reported in Europe and America. However, the emergence of linezolid resistance in <i>C. difficile</i> in the Asia-Pacific region and its impacts on <i>C. difficile</i> pathogenicity remain unclear. In this study, 881 <i>C. difficile</i> isolates from the Asia-Pacific region were screened for <i>cfr</i>-like genes. Whole genome sequencing was performed on 16 <i>cfr</i>-like gene-positive isolates from four countries. Thirteen isolates possessed <i>cfr</i>(B), which was located within Tn<i>6218</i>, while three isolates possessed <i>cfr</i>(C), which was located within the integrative and conjugative elements (ICE) F548 and DA275. Fourteen (87.5%, 14/16) of the <i>cfr</i>-like gene-positive isolates were resistant to linezolid. In comparison to the two isolates susceptible to linezolid, these 14 isolates exhibited significantly higher mRNA expression levels of <i>cfr</i>(B) and <i>cfr</i>(C), along with significantly higher bacterial density at 12 h. Conversely, they demonstrated reduced abilities for sporulation and biofilm formation. After the <i>cfr</i>(B) gene was knocked down by the CRISPR interference, the <i>C. difficile</i> strain presented lower bacterial density at 12 h, higher toxin production and stronger sporulation and biofilm formation abilities. Our findings reveal the emergence of <i>cfr</i>-like genes <i>C. difficile</i> isolates in the Asia-Pacific region, highlighting that <i>cfr</i>-like genes not only mediate linezolid resistance but also contribute to regulating pathogenic potential. Linezolid resistance in CDI should be closely monitored in specific patients.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2627070"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent neutralization of Rift Valley fever virus mediated by monoclonal antibodies via concurrent inhibition of attachment and fusion.","authors":"Meng Hao, Ting Bian, Zhengshan Chen, Guanying Zhang, Chuanyi Zhao, Guangcheng Fu, Yi Chen, Xiangyang Chi, Pengfei Fan, Ting Fang, Changming Yu, Jianmin Li","doi":"10.1080/22221751.2026.2623698","DOIUrl":"10.1080/22221751.2026.2623698","url":null,"abstract":"<p><p>Rift Valley fever virus (RVFV) is one of the most important mosquito-borne pathogens that causes substantial morbidity and mortality in livestock and humans. Despite its public health and economic impact, no licenced vaccines or therapeutics are currently available for human use. Here, we report the isolation of a panel of Gn-specific monoclonal antibodies (mAbs) from the memory B cells of rhesus macaques immunized with Ad4-GnGc or Ad5-GnGc. 20 mAbs with neutralizing activity were identified and divided into two groups, targeting subdomain I and subdomain III of the Gn protein, respectively. In murine infection models, representative nAbs A38 and A13 demonstrated efficacious protection against RVFV infection in both prophylactic and therapeutic settings. Research on the neutralizing mechanisms of antibodies revealed that A13 mainly mediates neutralization by inhibiting RVFV fusion to cells, while A38 disrupts multiple stages of the viral entry process by blocking both virus attachment and membrane fusion. To gain deeper insights into these mechanisms, we predicted the variable regions of antibodies and performed molecular docking with RVFV Gn head domain. Structural analysis showed that A38 binds to the DI and DIII subdomains, while A13 binds to an epitope spanning three subdomains of Gn, likely preventing the structural rearrangements required for membrane fusion. This study identifies multiple promising therapeutic candidates against RVFV and elucidates the structural mechanisms by which neutralizing antibodies inhibit various stages of the viral life cycle. These findings deepen our understanding of RVFV pathogenesis and will facilitate the development of novel therapeutic strategies.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"15 1","pages":"2623698"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12893178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA mediated expression of novel fusion phage tail protein with antimicrobial peptides inside macrophages for targeted clearance of intracellular <i>Mycobacterium tuberculosis</i>.","authors":"Ziwei Chen, Xueting Fan, Liying Zhou, Lihui Zou, Li Wan, Yayu Li, Chang Li, Lu Kuai, Jiahui Cai, Lili Zhang, Yifei Li, Hexin Li, Kanglin Wan, Haican Liu, Hongtao Xu, Fei Xiao","doi":"10.1080/22221751.2026.2627075","DOIUrl":"10.1080/22221751.2026.2627075","url":null,"abstract":"<p><p>Current anti-tuberculosis treatments primarily target extracellular <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), but exhibit limited efficacy against intracellular <i>Mtb</i>, leading to incomplete clearance of pathogens and an increased risk of recurrence. Antimicrobial peptides (AMPs) possess broad-spectrum antimicrobial activity and low potential for resistance development. Here we developed an <i>in vitro</i> mRNA expression platform which not only facilitates intracellular AMPs expression within macrophages, but also significantly enhances their bactericidal activity against <i>Mtb</i> post-infection. Notably, the combination of AMPs trimers demonstrated superior anti-<i>Mtb</i> activity compared to individual AMPs or other combinations. Furthermore, fusion of this AMP complex with either the minor tail protein Gp6 or lysin Gp10 from <i>Mycobacterium phage</i> L5 substantially improved macrophage-specific targeting and intracellular <i>Mtb</i> elimination. Thus, our current study provides novel insights and innovative strategies for the treatment of tuberculosis or other intracellular bacterial pathogens.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2627075"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Chikungunya virus infection and pregnancy outcomes: a global systematic review and meta-analysis of vertical transmission dynamics and associated morbidity.","authors":"Yan Guo, Yujie Xiang, Mengyuan Zheng, Zhouling Pan, Yanxian Jiang, Wei Chang, Gaowen Liu, Yonghan Luo, A-Mei Zhang, Li Liu, Yuanyuan Zhang, Caifen Zhu, Jie Zhang, Yue Feng, Xueshan Xia","doi":"10.1080/22221751.2026.2651466","DOIUrl":"10.1080/22221751.2026.2651466","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) infection during pregnancy presents a major threat to maternal-fetal health, yet a comprehensive global assessment of vertical transmission risks and perinatal outcomes remains scarce. To provide a comprehensive evidence synthesis, we conducted a systematic review and meta-analysis, prospectively registered in PROSPERO (CRD420251164423). We screened studies published up to October 20, 2025, and included 57 observational studies for qualitative synthesis, with 27 studies pooled in meta-analyses. The pooled vertical transmission rate was 18.1%, revealing a pronounced gestational-age gradient: rates were low in the first (3.9%) and second (1.2%) trimesters but surged dramatically during the third trimester (36.5%) and the intrapartum period (49.1%). Adverse pregnancy outcomes occurred in 11.3% of infected women, with abnormal fetal heart rate (44.9%) and stillbirth (22.0%) being the most frequent. Among neonates, 36.5% experienced adverse outcomes, commonly including feeding difficulties (79.4%), fever (68.9%), and thrombocytopenia (57.2%); neonatal mortality reached 6.9%. Crucially, meta-analysis of comparative studies demonstrated that maternal CHIKV infection was associated with a more than two-fold higher risk of adverse perinatal outcomes (OR = 2.28), with particularly robust associations identified for abnormal fetal heart rate (OR = 5.07) and delayed neurodevelopment (OR = 11.98). This study underscores that maternal CHIKV infection, especially during late gestation, substantially elevates the risks of vertical transmission and severe perinatal complications. Consequently, our findings strongly advocate for the implementation of enhanced prenatal surveillance and systematic postnatal assessment protocols in CHIKV-endemic regions to mitigate adverse outcomes and guide public health interventions.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2651466"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Rv1471-expressing chimpanzee adenovirus vaccine confers protection against tuberculosis by inducing alveolar macrophage trained immunity and polyfunctional T-cell responses.","authors":"Huiling Wang, Ying Zhang, Jianhui Li, Juan Wu, Shaoqiong Huang, Shiqi Xie, Xuejiao Huang, Jing Wang, Xiao-Yong Fan, Zhidong Hu","doi":"10.1080/22221751.2026.2637292","DOIUrl":"10.1080/22221751.2026.2637292","url":null,"abstract":"<p><p>The limited protection afforded by Bacille Calmette-Guérin (BCG) against pulmonary tuberculosis (TB) underscores the critical need for novel vaccine strategies. Alveolar macrophages (AMs), as the primary sentinel cells encountering inhaled <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), play a decisive role in early infection outcomes, yet their potential as a direct vaccine target remains largely untapped. Here, we developed a chimpanzee adenovirus vaccine expressing the <i>Mtb</i> antigen Rv1471 (rAd-Rv1471), which we previously identified for its unique capacity to induce innate immune memory. In murine models, intranasal rAd-Rv1471 administration reprogrammed AMs into a trained state, characterized by enhanced production of pro-inflammatory cytokines, elevated surface expression of MHC II and CD86, and improved cell-intrinsic control of intracellular mycobacterial growth. Transcriptomic analysis revealed upregulation of key immunometabolic pathways, including Akt/mTOR/HIF-1α signalling and glycolysis. Concurrently, intranasal rAd-Rv1471 administration induced potent antigen-specific, polyfunctional T cells in the lung. This dual engagement of innate and adaptive immunity conferred significant protection against aerosol <i>Mtb</i> challenge. Furthermore, rAd-Rv1471 acted as an effective heterologous booster, enhancing protection in BCG-primed mice. Our findings establish rAd-Rv1471 as a synergistic mucosal vaccine candidate that concurrently induces trained immunity in AMs and polyfunctional T-cell responses, highlighting a promising dual-targeting strategy for next-generation TB vaccines.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2637292"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a novel hybrid alphavirus-Nipah virus pseudovirion for rapid quantification of vaccine-induced neutralization antibodies.","authors":"Brian Hetrick, Sravya Sowdamini Nakka, Dongyang Yu, Sarah Swineford, Nadia Storm, Anthony Griffiths, Yuntao Wu","doi":"10.1080/22221751.2026.2660425","DOIUrl":"https://doi.org/10.1080/22221751.2026.2660425","url":null,"abstract":"<p><p>Nipah virus (NiV) is an emergent paramyxovirus that causes serious disease in humans and animals. Accurate quantification of neutralizing antibodies (nAB) against NiV is essential for vaccine development. The current standard, the plaque reduction neutralization test (PRNT), requires authentic infectious NiV and BSL-4 containment, taking 4-7 days to complete. In this study, we developed a hybrid alphavirus-Nipah virus pseudovirion (Ha-NiV) composed of a non-replicating Nipah virus virus-like particle (VLP) that encapsulates an RNA genome from a fast-expressing SFV (Semliki Forest Virus) alphaviral vector. Ha-NiV can infect NiV target cells but is replication incompetent, enabling rapid quantification of nAB (6-18 h) in BSL-2 conditions. We demonstrated concentration-dependent neutralization of Ha-NiV using an anti-NiV F glycoprotein antibody, 12B2, which is induced with a prefusion stabilized NiV F ectodomain trimer. We further validated the Ha-NiV-based neutralization assay using sera from Nipah virus-infected African green monkeys, and established a good correlation (<i>R</i>² = 0.86) with PRNT, demonstrating comparable specificity and sensitivity. These results demonstrate that the Ha-NiV assay can serve as a novel platform for convenient and rapid quantification of vaccine-induced nAB in BSL-2 settings.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"15 1","pages":"2660425"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymptomatic malaria: a hidden reservoir for the transmission and circulation of artemisinin partial-resistant <i>Plasmodium falciparum</i> in Tanzania.","authors":"Ernest Mazigo, Wang-Jong Lee, Hojong Jun, Fadhila Fitriana, Jadidan Hada Syahada, Johnsy Mary Louis, Fauzi Muh, Feng Lu, Kyu Joon Lee, Joo-Won Nam, Joon-Hee Han, Tae-Hyung Kwon, Se Jin Lee, Sunghun Na, Wanjoo Chun, Won Sun Park, Eun-Taek Han, Jim Todd, Alphaxard Manjurano, Winifrida Kidima, Jin-Hee Han","doi":"10.1080/22221751.2025.2602320","DOIUrl":"10.1080/22221751.2025.2602320","url":null,"abstract":"<p><p>Asymptomatic malaria infections contribute substantially to silent transmission, but the prevalence of artemisinin resistance (ART-R) markers in these carriers remains poorly understood. A community-based cross-sectional study was conducted in Tanzania from December 2022 to July 2023, enrolling 3,489 participants from high-transmission regions of Geita and Kigoma and a low-transmission region of Arusha. Four villages per region were randomly selected, and venous blood samples were tested using rapid diagnostic tests, microscopy, and qPCR, revealing overall positivity rate of 24.4%, 15.8%, and 26.2%, respectively, which indicate a significant proportion of submicroscopic infections. Among the 802 isolates successfully sequenced for <i>pfk13</i> and <i>pfmdr1</i>, 24 (3.0%) isolates from high-transmission areas carried validated <i>pfk13</i> partial-resistance markers Y493H (0.2%), R561H (2.0%), and A675V (0.7%), while all low-transmission isolates were wild-type. All isolates retained the <i>pfmdr1</i> N86 codon, and the NFD haplotype associated with reduced susceptibility to lumefantrine was detected in 48.1% and 48.4% of isolates in high- and low-transmission areas, respectively. Mutations were more frequent in children under five and in females. Artemether-lumefantrine (AL, 64.7%) was the most commonly used antimalarial in high-transmission areas, whereas sulfadoxine-pyrimethamine (SP, 75.9%) predominated in low-transmission areas. Higher AL use correlated with increased <i>pfmdr1</i> mutation prevalence in high-transmission regions, while NFD detection in low-transmission areas may reflect gene flow from high-transmission settings. These findings demonstrate that asymptomatic carriers are a substantial hidden reservoir of ART-resistant parasites, emphasizing the importance of integrating molecular surveillance and demographic information on asymptomatic infections into malaria control programs to detect emerging resistance and guide targeted interventions in Tanzania.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"15 1","pages":"2602320"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of the novel PA-D27G mutation conferring reduced baloxavir susceptibility in influenza A viruses circulating in China, 2018-2025.","authors":"Binhuang Sun, Yulei Sun, Hongyu Wang, Xiaolu Tang, Wanggang Tang, Yabo Mi, Zhouying Shen, Quanlin Xue, Yinying Lu, Xiaoyu Zhao, Jingwen Ai, Jian Lu, Wenhong Zhang","doi":"10.1080/22221751.2026.2620222","DOIUrl":"10.1080/22221751.2026.2620222","url":null,"abstract":"<p><p>Seasonal influenza A viruses evolve rapidly, yet the emergence and molecular basis of resistance to the polymerase acidic (PA) inhibitor baloxavir marboxil (BXM), which is widely used in China, remain elusive. To address this, 3938 PA gene sequences were collected from influenza patients across mainland China between 2018 and 2025, from the national surveillance network and GISAID. By screening post-market mutations in the N-terminal domain of PA (PAN) that appeared in at least two samples and at a frequency below 50%, twenty-five single-point mutations were identified and additionally six linked mutations potentially associated with drug pressure. The impact of these mutations on BXM sensitivity was subsequently evaluated. Our analysis revealed the emergence of known mutations associated with reduced BXM sensitivity, including L28P, K34R, E198 K, although their prevalence remained low (2/3850, 0.05%). Notably, we identified a novel substitution, D27G, which conferred an approximately 12.4-fold reduction in BXM susceptibility compared with the wild-type virus and exhibited higher replication fitness than the canonical resistance mutation I38T, as demonstrated in human airway organoids. Molecular dynamics simulations further indicated that PA-D27G attenuates the interaction between PA and baloxavir acid, the active form of BXM. Epidemiological analysis showed that D27G mutation remained rare, being detected in four isolates (4/1247, 0.32%) in mainland China, and at a sporadic prevalence (<0.1%, 9/53132) across global isolates. In conclusion, these results demonstrate the early emergence of BXM-associated resistance in China and identify PA-D27G as a resistance-associated mutation with preserved viral fitness, underscoring the importance of continued genomic and epidemiologic surveillance.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2620222"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}