Emerging Microbes & Infections最新文献

{"title":"The epidemiology and gene mutation characteristics of pyrazinamide-resistant <i>Mycobacterium tuberculosis</i> clinical isolates in Southern China.","authors":"Nan Wang, Fanrong Meng, Li Deng, Ling Wu, Yu Yang, Hua Li, Yuanjin Chen, Zeyou Wei, Bei Xie, Lan Gong, Qun Niu, Jie Lei, Junwen Gao, Bo Huang, Qi Wang, Xiaomin Lai, Zhihui Liu, Jinxing Hu","doi":"10.1080/22221751.2024.2447607","DOIUrl":"10.1080/22221751.2024.2447607","url":null,"abstract":"<p><p>This study investigates the epidemic trend of pyrazinamide (PZA)-resistant tuberculosis in Southern China over 11 years (2012-2022) and evaluates the mutation characteristics of PZA resistance-related genes (<i>pncA, rpsA,</i> and <i>panD</i>) in clinical <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) isolates. To fulfil these goals, we analyzed the phenotypic PZA resistance characteristics of 14,927 clinical isolates for which Bactec MGIT 960 PZA drug susceptibility testing (DST) results were available, revealing that 2,054 (13.76%) isolates were resistant to PZA. After evaluating the annual variation in the PZA resistance rate among tuberculosis cases in this region, it was observed that it decreased from 37.21% to 6.45% throughout the initial 7 years (2012-2018) and then increased from 8.01% to 12.12% over the subsequent 4 years (2019-2022). Sequences of <i>pncA</i> were obtained from 402 clinical <i>M. tuberculosis</i> complex isolates. For <i>rpsA</i> and <i>panD,</i> sequences were obtained from 360 clinical <i>M. tuberculosis</i> complex isolates. Mutations in <i>pncA</i> were found in 8 out of 223 PZA-sensitive isolates (3.59%) and 105 of 179 (58.66%) PZA-resistant isolates. Conversely, non-synonymous mutations in <i>rpsA</i> were identified in 5 of 137 (3.65%) PZA-resistant isolates, whereas the mutation ratio of <i>rpsA</i> among PZA-sensitive isolates was high at 14.03% (31/221). This difference in the <i>rpsA</i> mutation rate was statistically significant (<i>P = 0.001</i>, chi-square test). No <i>panD</i> mutations were observed in the 137 PZA-resistant isolates, whereas two PZA-sensitive isolates harboured point mutations in <i>panD</i>, including one nonsense mutation (C433 T) and another C-69 T mutation. These findings indicate that <i>rpsA</i> and <i>panD</i> may not significantly contribute to the development of PZA resistance in clinical <i>M. tuberculosis</i> isolates.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2447607"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913559","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":"Correction.","authors":"","doi":"10.1080/22221751.2025.2467547","DOIUrl":"10.1080/22221751.2025.2467547","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"14 1","pages":"2467547"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472395","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":"Hypermutability of <i>Mycolicibacterium smegmatis</i> due to ribonucleotide reductase-mediated oxidative homeostasis and imbalanced dNTP pools.","authors":"Xiao Zhang, Yuchang Di, Yu Zhang, Youwei Hu, Mingzhe Chi, Jian Kang, Yuqing Zheng, Hengyu Wang, Yu Wang, Jiazhen Chen, Xuelian Zhang","doi":"10.1080/22221751.2025.2480698","DOIUrl":"10.1080/22221751.2025.2480698","url":null,"abstract":"<p><p>Ribonucleotide reductase (RNR) catalyzes the synthesis of four deoxyribonucleoside triphosphates (dNTPs), which are essential for DNA replication. Although dNTP imbalances reduce replication fidelity and elevate mutation rates, the impact of RNR dysfunction on Mycobacterium tuberculosis (Mtb) physiology and drug resistance remains unknown. Here, we constructed inducible knockdown strains for the RNR R1 subunit NrdE in Mtb and Mycolicibacterium smegmatis (Msm). NrdE knockdown significantly impaired growth and metabolic imbalances, indirectly disrupting oxidative homeostasis and mycolic acid synthesis, while increasing levels of intracellular ROS accumulation and enhancing cell wall permeability. Additionally, we developed genomic mutant strains, Msm-Y252A and Msm-Q255A, featuring targeted point mutations in the substrate-specific site (S-site) of the RNR loop domain, which determines NDP reduction specificity. The Msm-Y252A displayed a 1.9-fold decrease in dATP and increases in dGTP (1.6-fold), dTTP (9.0-fold), and dCTP (1.3-fold). In contrast, Msm-Q255A exhibited elevated intracellular levels of dGTP (1.6-fold), dTTP (6.1-fold), and dATP (1.5-fold), while dCTP levels remained unchanged. Neither the NrdE knockdown strain nor the S-site mutants exhibited direct resistance development; however, they both showed genomic instability, enhancing the emergence of rifampicin-resistant mutants, even with a 70-fold and a 25-fold increase in mutation frequency for Msm-Y252A and Msm-Q255A, respectively. This study demonstrates that NrdE is integral to Mycobacterium survival and genomic stability and that its RNR dysfunction creates a mutagenic environment under selective pressure, indirectly contributes to the development of drug resistance, positioning NrdE as an effective target for therapeutic strategies and a valuable molecular marker for early detection of drug-resistant Mtb.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2480698"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647678","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":"Transmissible <i>Staphylococcus pseudintermedius</i> thwarts neutrophil extracellular trap-driven containment to promote invasive disease.","authors":"Rita Haller, Yiyang Cai, Nicole de Buhr, Johanna C Rieder, Dirk Schlüter, Claas Baier, Holger Rohde, Maren von Köckritz-Blickwede, Marius Vital, Volker Winstel","doi":"10.1080/22221751.2025.2482709","DOIUrl":"10.1080/22221751.2025.2482709","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus pseudintermedius</i> (MRSP) is an emerging zoonotic pathogen that causes a variety of clinical diseases in mammalian hosts. While it frequently causes infections in dogs and other domestic animals, accumulating evidence indicates that zoonotic spillover and cross-species transmission events favour local and invasive <i>S. pseudintermedius</i> infections in humans. However, immuno-evasive maneuvers that shape <i>S. pseudintermedius</i> pathogenicity and survival in diseased hosts remain enigmatic. Powered by multi-tech imaging and a mouse model of bloodstream infection, we illustrate that <i>S. pseudintermedius</i> adopted a virulence mechanism from predominant bacterial pathogens to surmount neutrophilic responses and neutrophil extracellular trap (NET)-mediated killing. Specifically, release of NucB, a thermostable nuclease, helps MRSP coping with the antimicrobial and pathogen-immobilizing properties of NETs and even promotes intra-neutrophil survival upon phagocytosis, thereby contributing to <i>S. pseudintermedius</i> pathogenesis and persistence within hepatic abscesses. Combined with the analysis of genetically distinct human clinical isolates, all of which display nuclease activity and features of resistance to NETosis-induced killing, our data highlight how zoonotic staphylococci overcome innate immune responses and concurrently uncover a mechanism that may exacerbate animal-borne MRSP infections in humans.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2482709"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763117","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":"Deciphering novel enzymatic and non-enzymatic lysine lactylation in <i>Salmonella</i>.","authors":"Chuanzhen Zhang, Tao Zhou, Chengxi Li, Danni Wang, Jing Tao, Xiaocen Zhu, Jie Lu, Jinjing Ni, Yu-Feng Yao","doi":"10.1080/22221751.2025.2475838","DOIUrl":"10.1080/22221751.2025.2475838","url":null,"abstract":"<p><p>Lysine lactylation, a novel post-translational modification, is involved in multiple cellular processes. The role of lactylation remains largely unknown, especially in bacteria. Here, we identified 1090 lactylation sites on 469 proteins by mass spectrometry in <i>Salmonella</i> Typhimurium. Many proteins involved in metabolic processes, protein translation, and other biological functions are lactylated, with lactylation levels varying according to the growth phase or lactate supplementation. Lactylation is regulated by glycolysis, and inhibition of L-lactate utilization can enhance lactylation levels. In addition to the known lactylase in <i>E. coli</i>, the acetyltransferase YfiQ can also catalyse lactylation. More importantly, L-lactyl coenzyme A (L-La-CoA) and <i>S,D</i>-lactoylglutathione (LGSH) can directly donate lactyl groups to target proteins for chemical lactylation. Lactylation is involved in <i>Salmonella</i> invasion of eukaryotic cells, suggesting that lactylation is crucial for bacterial virulence. Collectively, we have comprehensively investigated protein lactylome and the regulatory mechanisms of lactylation in <i>Salmonella</i>, providing valuable insights into studying lactylation function across diverse bacterial species.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2475838"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540594","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":"Emerging antifungal resistance in <i>Trichophyton mentagrophytes</i>: insights from susceptibility profiling and genetic mutation analysis.","authors":"Yakun Shao, Jin Shao, Sybren de Hoog, Paul Verweij, Lin Bai, Riina Richardson, Malcolm Richardson, Zhe Wan, Ruoyu Li, Jin Yu, Yinggai Song","doi":"10.1080/22221751.2025.2450026","DOIUrl":"10.1080/22221751.2025.2450026","url":null,"abstract":"<p><p><b>ABSTRACT</b><i>Trichophyton</i> species, the leading cause of dermatophytosis globally, are increasingly resistant to antifungal treatments, concerns about effective management strategies. In light of the absence of established resistance criteria for terbinafine and azoles, coupled with a dearth of research on resistance mechanisms in <i>Trichophyton</i>, antifungal susceptibility and drug resistance gene diversity were analyzed across 64 <i>T. mentagrophytes</i>, 65 <i>T. interdigitale</i>, and 2 <i>T. indotineae</i> isolates collected in China between 1999 and 2024 and 101 published <i>T. indotineae</i> strains. Analyses of the minimum inhibitory concentrations (MICs) of terbinafine, itraconazole, voriconazole, posaconazole, and isavuconazole revealed a concerning increase in <i>T. indotineae</i> with terbinafine resistance, including two novel isolates from China. Compared with <i>T. interdigitale, T. mentagrophytes</i> presented higher terbinafine MICs but similar azole susceptibility. Notably, 27 <i>T. interdigitale</i> isolates were classified as non-wild-type for terbinafine. Genetic diversity was analyzed for the <i>SQLE</i>, <i>CYP51A</i> and <i>CYP51B</i> gene. Specifically, <i>T. indotineae</i> isolates presented SQLE protein changes linked to terbinafine resistance. SQLE diversity was linked to terbinafine sensitivity, whereas alterations in CYP51A were associated with itraconazole sensitivity, with notable statistical significance evident across various protein isoforms. The relationship between protein diversity and drug sensitivity is presented in detail. Together, these findings highlight a growing prevalence of antibiotic resistance among <i>Trichophyton</i> and identify potential target genes for new therapies, underscoring the need for ongoing monitoring and offering directions for novel therapeutics.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2450026"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920841","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":"Pathogenicity and transmissibility of bovine-derived HPAI H5N1 B3.13 virus in pigs.","authors":"Taeyong Kwon, Jessie D Trujillo, Mariano Carossino, Heather M Machkovech, Konner Cool, Eu Lim Lyoo, Gagandeep Singh, Sujan Kafle, Shanmugasundaram Elango, Govindsamy Vediyappan, Wanting Wei, Nicholas Minor, Franco S Matias-Ferreyra, Igor Morozov, Natasha N Gaudreault, Udeni B R Balasuriya, Lisa E Hensley, Diego G Diel, Wenjun Ma, Thomas C Friedrich, Juergen A Richt","doi":"10.1080/22221751.2025.2509742","DOIUrl":"10.1080/22221751.2025.2509742","url":null,"abstract":"<p><p>Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle, the virus has continued to spread, reaching 17 states and at least 1000 dairy herds in the United States. Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important host in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated. Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus. Infectious virus and viral antigen were mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points, suggesting replication of the bovine-derived HPAI H5N1 B3.13 virus in pigs. In one animal, we detected the emergence of a mutation in the hemagglutinin (HA) previously associated with increased affinity for \"mammalian-type\" α2,6-linked sialic acid receptors, but this mutation did not reach majority consensus levels. Sentinel contact pigs remained sero-negative throughout the study, indicating lack of transmission. These results support that pigs are susceptible to a bovine-derived HPAI H5N1 B3.13 virus, but this virus did not replicate as robustly in pigs as swine-adapted influenza viruses.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2509742"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110059","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 haemagglutinin gene of bovine-origin H5N1 influenza viruses currently retains receptor-binding and pH-fusion characteristics of avian host phenotype.","authors":"Jiayun Yang, Mehnaz Qureshi, Reddy Kolli, Thomas P Peacock, Jean-Remy Sadeyen, Toby Carter, Samuel Richardson, Rebecca Daines, Wendy S Barclay, Ian H Brown, Munir Iqbal","doi":"10.1080/22221751.2025.2451052","DOIUrl":"10.1080/22221751.2025.2451052","url":null,"abstract":"<p><p>Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has caused a panzootic affecting all continents except Australia, expanding its host range to several mammalian species. In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. Over 891 dairy farms across 16 states have tested positive until 25 December 2024, with zoonotic infections reported among dairy workers. This raises concerns about the virus undergoing evolutionary changes in cattle that could enhance its zoonotic potential. The Influenza glycoprotein haemagglutinin (HA) facilitates entry into host cells through receptor binding and pH-induced fusion with cellular membranes. Adaptive changes in HA modulate virus-host cell interactions. This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1 in the United Kingdom, focusing on receptor binding, pH fusion, and thermostability. All the tested H5N1 viruses showed binding exclusively to avian-like receptors, with a pH fusion of 5.9, outside the pH range associated with efficient human airborne transmissibility (pH 5.0-5.5). We further investigated the impact of emerging HA substitutions seen in the ongoing cattle outbreaks, but saw little phenotypic difference, with continued exclusive binding to avian-like receptor analogues and pHs of fusion above 5.8. This suggests that the HA genes from the cattle and goat outbreaks do not pose an enhanced threat compared to circulating avian viruses. However, given the rapid evolution of H5 viruses, continuous monitoring and updated risk assessments remain essential to understanding virus zoonotic and pandemic risks.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2451052"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970155","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":"Unique immune and other responses of human nasal epithelial cells infected with H5N1 avian influenza virus compared to seasonal human influenza A and B viruses.","authors":"Kai Sen Tan, Jing Liu, Anand Kumar Andiappan, Zhe Zhang Ryan Lew, Ting Ting He, Hsiao Hui Ong, Douglas Jie Wen Tay, Zhen Qin Aw, Bowen Yi, Arfah Mohd Fauzi, Thinesshwary Yogarajah, Lee Ching Pei Carmen, Justin Jang Hann Chu, Vincent T Chow, Mookkan Prabakaran, De-Yun Wang","doi":"10.1080/22221751.2025.2484330","DOIUrl":"10.1080/22221751.2025.2484330","url":null,"abstract":"<p><p>Highly pathogenic avian influenza (HPAI) virus (e.g. H5N1) infects the lower airway to cause severe infections, and constitute a prime candidate for the emergence of disease X. The nasal epithelium is the primary portal of entry for respiratory pathogens, serving as the airway's physical and immune barrier. While HPAI virus predominantly infects the lower airway, not much is known about its interactions with the nasal epithelium. Hence, we sought to elucidate and compare the differential responses of the nasal epithelium against HPAI infection that may contribute to its pathology, and to identify critical response markers. We infected human nasal epithelial cells (hNECs) cultured at the air-liquid interface from multiple healthy donors with clinical isolates of major human seasonal influenza viruses (H1N1, H3N2, influenza B) and HPAI H5N1. The infected cells were subjected to virologic, transcriptomic and secretory protein analyses. While less adapted to infecting the nasal epithelium, HPAI H5N1 elicited unique host responses unlike seasonal influenza. Interestingly, H5N1 infection of hNECs induced responses indicative of subdued antiviral activity (e.g. reduced expression of IFNβ, and inflammasome mediators, IL-1α and IL-1β); decreased wound healing; suppressed re-epithelialization; compromised epithelial barrier integrity; diminished responses to oxidative stress; and increased transmembrane solute and ion carrier gene expression. These unique molecular changes in response to H5N1 infection may represent potential targets for enhancing diagnostic and therapeutic strategies for better surveillance and management of HPAI infection in humans.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2484330"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691586","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":"Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States.","authors":"Ahmed Mostafa, Ramya S Barre, Anna Allué-Guardia, Ruby A Escobedo, Vinay Shivanna, Hussin Rothan, Esteban M Castro, Yao Ma, Anastasija Cupic, Nathaniel Jackson, Mahmoud Bayoumi, Jordi B Torrelles, Chengjin Ye, Adolfo García-Sastre, Luis Martinez-Sobrido","doi":"10.1080/22221751.2024.2447614","DOIUrl":"10.1080/22221751.2024.2447614","url":null,"abstract":"<p><p>The host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States (US). Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified in dairy cattle and human, respectively, and their low pathogenic forms, rLPbTX and rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Still, variations in the PA and NA proteins didn't affect their antiviral susceptibility to PA and NA inhibitors. Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice. The lungs of rHPhTX-infected mice produced higher inflammatory cytokines/chemokines than rHPbTX-infected mice. Our results highlight the potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak in the US.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2447614"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893000","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}