Nature Microbiology最新文献

{"title":"Multinational epidemiological analysis of oral human papillomavirus incidence in 3,137 men","authors":"Racheal S. Dube Mandishora, Brittney L. Dickey, Wenyi Fan, Bradley Sirak, Kimberly Isaacs-Soriano, Julie Rathwell, Martha Abrahamsen, Richard R. Reich, Michael J. Schell, Eduardo Lazcano-Ponce, Luisa L. Villa, Anna R. Giuliano","doi":"10.1038/s41564-024-01824-5","DOIUrl":"10.1038/s41564-024-01824-5","url":null,"abstract":"Oral human papillomavirus (HPV) is associated with oropharyngeal cancer (OPC). Although OPC incidence is increasing globally, knowledge of oral HPV infection rates is limited. Here we carried out an observational epidemiological analysis of oral HPV incidence in 3,137 men enrolled from the United States, Mexico and Brazil between 2005 and 2009. Individuals were followed for new HPV infection for a median of 57 months. Cumulative incidence and factors associated with acquisition were also assessed. The incidence rate of oral oncogenic HPV was 2.4 per 1,000 person-months, did not vary with age and was constant throughout the study period. Risk of oral HPV acquisition was significantly associated with alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment. These data indicate that men are at risk of acquiring oral HPV throughout their lifetime, suggesting that catch-up vaccination may reduce new infection incidence. Multinational analysis of oral human papillomavirus infection incidence and associated factors in 3,137 men reveals infection risk is maintained throughout lifetime, with implications for vaccination strategies.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2836-2846"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2","authors":"Rui Zhu, Yuanyuan Wu, Yang Huang, Yanan Jiang, Yichao Jiang, Dongqing Zhang, Hui Sun, Zhenhong Zhou, Lizhi Zhou, Shihan Weng, Hao Chen, Xiaoqing Chen, Wenjing Ning, Yuxiang Zou, Maozhou He, Hongwei Yang, Weixi Deng, Yu Li, Zhenqin Chen, Xiangzhong Ye, Jinle Han, Zhichao Yin, Huan Zhao, Che Liu, Yuqiong Que, Mujin Fang, Hai Yu, Jun Zhang, Wenxin Luo, Shaowei Li, Qingbing Zheng, Longfa Xu, Ningshao Xia, Tong Cheng","doi":"10.1038/s41564-024-01822-7","DOIUrl":"10.1038/s41564-024-01822-7","url":null,"abstract":"Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus–receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion–SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine. Identification of a broadly therapeutic antibody h1A6.2 against enteroviruses, which mimics the entry receptor SCARB2 and triggers monocyte/macrophage-dependent Fc effector functions in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2939-2953"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with oral HPV infection among a large multinational cohort of men","authors":"","doi":"10.1038/s41564-024-01834-3","DOIUrl":"10.1038/s41564-024-01834-3","url":null,"abstract":"We show that men from the USA, Mexico and Brazil are at risk of acquiring oral human papillomavirus (HPV) throughout their lifetime. Risk factors for new HPV infections are alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2801-2802"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Pathogen genomic surveillance status among lower resource settings in Asia","authors":"Marya Getchell, Suci Wulandari, Ruklanthi de Alwis, Shreya Agoramurthy, Yoong Khean Khoo, Tze-Minn Mak, La Moe, Anne-Claire Stona, Junxiong Pang, Muhd Haziq Fikry Haji Abdul Momin, Afreenish Amir, Lucia Rizka Andalucia, Ghows Azzam, Savuth Chin, Thanat Chookajorn, Govindakarnavar Arunkumar, Do Thai Hung, Aamer Ikram, Runa Jha, Erik A. Karlsson, Mai Quynh Le Thi, Surakameth Mahasirimongkol, Gathsaurie Neelika Malavige, Jessica E. Manning, Syarifah Liza Munira, Nguyen Vu Trung, Imran Nisar, Firdausi Qadri, Farah Naz Qamar, Matthew T. Robinson, Cynthia P. Saloma, Swe Setk, Tahmina Shirin, Le Van Tan, Timothy John R. Dizon, Ravindran Thayan, Hlaing Myat Thu, Hasitha Tissera, Phonepadith Xangsayarath, Zainun Zaini, John C. W. Lim, Sebastian Maurer-Stroh, Gavin J. D. Smith, Lin-Fa Wang, Paul Pronyk, on behalf of the Asia Pathogen Genomics Initiative (Asia PGI) consortium","doi":"10.1038/s41564-024-01848-x","DOIUrl":"10.1038/s41564-024-01848-x","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"258-258"},"PeriodicalIF":20.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01848-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vibrio cholerae virulence is blocked by chitosan oligosaccharide-mediated inhibition of ChsR activity","authors":"Yutao Liu, Jialin Wu, Ruiying Liu, Fan Li, Leyan Xuan, Qian Wang, Dan Li, XinTong Chen, Hao Sun, Xiaoya Li, Chen Jin, Di Huang, Linxing Li, Guosheng Tang, Bin Liu","doi":"10.1038/s41564-024-01823-6","DOIUrl":"10.1038/s41564-024-01823-6","url":null,"abstract":"Vibrio cholerae causes cholera, an important cause of death worldwide. A fuller understanding of how virulence is regulated offers the potential for developing virulence inhibitors, regarded as efficient therapeutic alternatives for cholera treatment. Here we show using competitive infections of wild-type and mutant bacteria that the regulator of chitosan utilization, ChsR, increases V. cholerae virulence in vivo. Mechanistically, RNA sequencing, chromatin immunoprecipitation with sequencing and molecular biology approaches revealed that ChsR directly upregulated the expression of the virulence regulator, TcpP, which promoted expression of the cholera toxin and the toxin co-regulated pilus, in response to low O2 levels in the small intestine. We also found that chitosan degradation products inhibit the ChsR–tcpP promoter interaction. Consistently, administration of chitosan oligosaccharide, particularly when delivered via sodium alginate microsphere carriers, reduced V. cholerae intestinal colonization and disease severity in mice by blocking the chsR-mediated pathway. These data reveal the potential of chitosan oligosaccharide as supplemental therapy for cholera treatment and prevention. The chitosan utilization regulator, ChsR, positively regulates Vibrio cholerae virulence factor expression, which can be inhibited therapeutically by chitosan oligosaccharide administration in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2909-2922"},"PeriodicalIF":20.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology","authors":"Ítalo Araújo Castro, Yanling Yang, Victoria Gnazzo, Do-Hyun Kim, Steven J. Van Dyken, Carolina B. López","doi":"10.1038/s41564-024-01852-1","DOIUrl":"10.1038/s41564-024-01852-1","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"259-259"},"PeriodicalIF":20.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01852-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and functional characterization of the Atlantic salmon gut microbiome in relation to nutrition and health","authors":"Arturo Vera-Ponce de León, Tim Hensen, Matthias Hoetzinger, Shashank Gupta, Bronson Weston, Sander M. Johnsen, Jacob A. Rasmussen, Cecilie Grønlund Clausen, Louisa Pless, Ana Raquel Andrade Veríssimo, Knut Rudi, Lars Snipen, Christian René Karlsen, Morten T. Limborg, Stefan Bertilsson, Ines Thiele, Torgeir R. Hvidsten, Simen R. Sandve, Phillip B. Pope, Sabina Leanti La Rosa","doi":"10.1038/s41564-024-01830-7","DOIUrl":"10.1038/s41564-024-01830-7","url":null,"abstract":"To ensure sustainable aquaculture, it is essential to understand the path ‘from feed to fish’, whereby the gut microbiome plays an important role in digestion and metabolism, ultimately influencing host health and growth. Previous work has reported the taxonomic composition of the Atlantic salmon (Salmo salar) gut microbiome; however, functional insights are lacking. Here we present the Salmon Microbial Genome Atlas consisting of 211 high-quality bacterial genomes, recovered by cultivation (n = 131) and gut metagenomics (n = 80) from wild and farmed fish both in freshwater and seawater. Bacterial genomes were taxonomically assigned to 14 different orders, including 35 distinctive genera and 29 previously undescribed species. Using metatranscriptomics, we functionally characterized key bacterial populations, across five phyla, in the salmon gut. This included the ability to degrade diet-derived fibres and release vitamins and other exometabolites with known beneficial effects, which was supported by genome-scale metabolic modelling and in vitro cultivation of selected bacterial species coupled with untargeted metabolomic studies. Together, the Salmon Microbial Genome Atlas provides a genomic and functional resource to enable future studies on salmon nutrition and health. Using shotgun metagenomics, cultivation and metabolic modelling, the authors construct the Salmon Microbial Genome Atlas as a resource for future studies on sustainable aquaculture.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3059-3074"},"PeriodicalIF":20.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the HPV types causing cervical cancer","authors":"Fernando Dias Gonçalves Lima, Mariano A. Molina","doi":"10.1038/s41564-024-01835-2","DOIUrl":"10.1038/s41564-024-01835-2","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2795-2796"},"PeriodicalIF":20.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost","authors":"Camille Bédard, Isabelle Gagnon-Arsenault, Jonathan Boisvert, Samuel Plante, Alexandre K. Dubé, Alicia Pageau, Anna Fijarczyk, Jehoshua Sharma, Laetitia Maroc, Rebecca S. Shapiro, Christian R. Landry","doi":"10.1038/s41564-024-01819-2","DOIUrl":"10.1038/s41564-024-01819-2","url":null,"abstract":"Azole antifungals are the main drugs used to treat fungal infections. Amino acid substitutions in the drug target Erg11 (Cyp51) are a common resistance mechanism in pathogenic yeasts. How many and which mutations confer resistance is, however, largely unknown. Here we measure the impact of nearly 4,000 amino acid variants of Candida albicans Erg11 on the susceptibility to six clinical azoles. This was achieved by deep mutational scanning of CaErg11 expressed in Saccharomyces cerevisiae. We find that a large fraction of mutations lead to resistance (33%), most resistance mutations confer cross-resistance (88%) and only a handful of resistance mutations show a significant fitness cost (9%). Our results reveal that resistance to azoles can arise through a large set of mutations and this will probably lead to azole pan-resistance, with little evolutionary compromise. This resource will help inform treatment choices in clinical settings and guide the development of new drugs. Deep mutational scanning of the azole antifungals drug target Erg11 provides an extensive catalogue of resistance mutations and reveals that resistance to azoles can arise through a large set of mutations that will probably lead to azole pan-resistance without a fitness cost.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3025-3040"},"PeriodicalIF":20.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis","authors":"Ujjini H. Manjunatha, Suresh B. Lakshminarayana, Rajiv S. Jumani, Alexander T. Chao, Joseph M. Young, Jonathan E. Gable, Mark Knapp, Imad Hanna, Jean-Rene Galarneau, John Cantwell, Upendra Kulkarni, Michael Turner, Peichao Lu, Kristen H. Darrell, Lucy C. Watson, Katherine Chan, Debjani Patra, Mulugeta Mamo, Catherine Luu, Carlos Cuellar, Jacob Shaul, Linda Xiao, Ying-Bo Chen, Shannon K. Carney, Jay Lakshman, Colin S. Osborne, Jennifer A. Zambriski, Natasha Aziz, Christopher Sarko, Thierry T. Diagana","doi":"10.1038/s41564-024-01810-x","DOIUrl":"10.1038/s41564-024-01810-x","url":null,"abstract":"Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site. EDI048 is orally efficacious in an immunocompromised mouse model despite negligible circulating concentrations, thus demonstrating that gastrointestinal exposure is necessary and sufficient for efficacy. In neonatal calves, a clinical model of cryptosporidiosis, EDI048 treatment resulted in rapid resolution of diarrhoea and significant reduction in faecal oocyst shedding. Safety and pharmacological studies demonstrated predictable metabolism and low systemic exposure of EDI048, providing a substantial safety margin required for a paediatric indication. EDI048 is a promising clinical candidate for the treatment of life-threatening paediatric cryptosporidiosis. EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2817-2835"},"PeriodicalIF":20.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01810-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}