Laura A. Hug, Roland Hatzenpichler, Cristina Moraru, André R. Soares, Folker Meyer, Anke Heyder, The Data Reuse Consortium, Alexander J. Probst
{"title":"A roadmap for equitable reuse of public microbiome data","authors":"Laura A. Hug, Roland Hatzenpichler, Cristina Moraru, André R. Soares, Folker Meyer, Anke Heyder, The Data Reuse Consortium, Alexander J. Probst","doi":"10.1038/s41564-025-02116-2","DOIUrl":"10.1038/s41564-025-02116-2","url":null,"abstract":"Science benefits from rapid open data sharing, but current guidelines for data reuse were established two decades ago, when databases were several million times smaller than they are today. These guidelines are largely unfamiliar to the scientific community, and, owing to the rapid increase in biological data generated in the past decade, they are also outdated. As a result, there is a lack of community standards suited to the current landscape and inconsistent implementation of data sharing policies across institutions. Here we discuss current sequence data sharing policies and their benefits and drawbacks, and present a roadmap to establish guidelines for equitable sequence data reuse, developed in consultation with a data consortium of 167 microbiome scientists. We propose the use of a Data Reuse Information (DRI) tag for public sequence data, which will be associated with at least one Open Researcher and Contributor ID (ORCID) account. The machine-readable DRI tag indicates that the data creators prefer to be contacted before data reuse, and simultaneously provides data consumers with a mechanism to get in touch with the data creators. The DRI aims to facilitate and foster collaborations, and serve as a guideline that can be expanded to other data types. In this Consensus Statement, a consortium of microbiome scientists discuss current sequencing data sharing policies and propose the use of a Data Reuse Information (DRI) tag to promote equitable and collaborative data sharing.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2384-2395"},"PeriodicalIF":19.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02116-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176633","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}
Leah M. Plasek Hegde, Lalith S. Gunawardane, Farshad Niazi, Uri Mbonye, Konstantin Leskov, Gani Perez, Curtis Dobrowolski, Meenakshi Shukla, William S. Nutt, Jonathan Karn, Saba Valadkhan
{"title":"HIV infection reprogrammes CD4+ T cells for quiescence and entry into proviral latency","authors":"Leah M. Plasek Hegde, Lalith S. Gunawardane, Farshad Niazi, Uri Mbonye, Konstantin Leskov, Gani Perez, Curtis Dobrowolski, Meenakshi Shukla, William S. Nutt, Jonathan Karn, Saba Valadkhan","doi":"10.1038/s41564-025-02128-y","DOIUrl":"10.1038/s41564-025-02128-y","url":null,"abstract":"Human immunodeficiency virus (HIV) persists in infected individuals despite effective antiretroviral therapy due to the rapid establishment of latent reservoirs, mainly composed of quiescent memory CD4+ T cells. The mechanisms governing latent reservoir formation remain poorly understood. Here, using single-cell RNA-seq and functional studies in human primary CD4+ T cell models, we show that HIV infection with reporter constructs and laboratory and patient-derived strains triggers transcriptomic remodelling, activating the p53 pathway and a quiescence programme mediated by Krüppel-like factor 2 (KLF2), a key quiescence regulator. Loss- and gain-of-function studies, including unbiased shRNA screens and confirmatory studies in CD4+ T cells from HIV+ donors, demonstrate that HIV infection drives KLF2 and p53 signalling, which downregulate MYC and proliferation pathways, resulting in proviral transcriptional silencing. This enhances latent reservoir formation in T cells, ensuring viral persistence. These findings present a mechanism for forming the latent HIV reservoir and broaden the repertoire of strategies through which viruses control host cells to their advantage. HIV infection triggers transcriptomic remodelling and a quiescence programme via KLF2 and the p53 pathway leading to proviral silencing.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2454-2471"},"PeriodicalIF":19.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02128-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153415","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}
Ricardo Fróis-Martins, Julia Lagler, Tim B. Schille, Osama Elshafee, Kontxi Martinez de San Vicente, Sarah Mertens, Michelle Stokmaier, Iman Kilb, Natacha Sertour, Sophie Bachellier-Bassi, Selene Mogavero, Dominique Sanglard, Christophe d’Enfert, Bernhard Hube, Salomé LeibundGut-Landmann
{"title":"Dynamic expression of candidalysin facilitates oral colonization of Candida albicans in mice","authors":"Ricardo Fróis-Martins, Julia Lagler, Tim B. Schille, Osama Elshafee, Kontxi Martinez de San Vicente, Sarah Mertens, Michelle Stokmaier, Iman Kilb, Natacha Sertour, Sophie Bachellier-Bassi, Selene Mogavero, Dominique Sanglard, Christophe d’Enfert, Bernhard Hube, Salomé LeibundGut-Landmann","doi":"10.1038/s41564-025-02122-4","DOIUrl":"10.1038/s41564-025-02122-4","url":null,"abstract":"Candida albicans is a common fungal member of the human microbiota but can also cause infections via expression of virulence factors associated with the yeast-to-hyphae transition. The evolutionary selection pressure to retain these pathogenic traits for a commensal microorganism remains unclear. Here we show that filamentation and hyphae-associated factors, including the toxin candidalysin, are crucial for colonization of the oral cavity, a major reservoir of C. albicans. Low-virulent strains of C. albicans expressed the candidalysin-encoding gene ECE1 transiently upon exposure to keratinocytes in vitro. In mice, ECE1 mutants were defective at accessing terminally differentiated oral epithelial layers where the fungus is protected from IL-17-mediated immune defence. Tight regulation of ECE1 expression prevented detrimental effects of candidalysin on the host. Our results suggest that hyphae-associated factors such as candidalysin govern not only pathogenicity, but also mucosal colonization through direct host interactions enabling C. albicans to create and maintain its niche in the oral mucosa. Despite being a virulence factor, candidalysin toxin is essential for Candida albicans to penetrate the oral epithelium to establish and maintain non-infectious colonization","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2472-2485"},"PeriodicalIF":19.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02122-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140242","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":"Metabolic regulation of host defence against viral infection through sensing oxaloacetate","authors":"","doi":"10.1038/s41564-025-02129-x","DOIUrl":"10.1038/s41564-025-02129-x","url":null,"abstract":"Metabolic pathways are important for all biological processes, including host defence against pathogens. We show that activation of innate immune signalling is primed by oxaloacetate sensing through the cytosolic malate dehydrogenase MDH1, ensuring optimal production of type I interferons and host immune homeostasis in response to influenza virus infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2367-2368"},"PeriodicalIF":19.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140444","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":"Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections.","authors":"Dinesh Subedi,Fernando Gordillo Altamirano,Rylee Deehan,Avindya Perera,Ruzeen Patwa,Xenia Kostoulias,Denis Korneev,Luke Blakeway,Nenad Macesic,Anton Y Peleg,Jeremy J Barr","doi":"10.1038/s41564-025-02130-4","DOIUrl":"https://doi.org/10.1038/s41564-025-02130-4","url":null,"abstract":"The Alfred Hospital in Melbourne, Australia, has reported an ongoing outbreak of infections caused by multidrug-resistant Enterobacter cloacae complex (ECC). Phage therapy is a promising strategy to treat antimicrobial-resistant infections. Utilizing the hospital's isolate collection, built over the past decade, we established an initial 3-phage cocktail with 54% ECC coverage. We then iteratively improved this product by enhancing phage killing efficiency using phage adaptation and expanded host range through targeted phage isolation against low-coverage ECC isolates. This optimization yielded Entelli-02, containing five well-characterized virulent phages that target clinical ECC isolates via distinct bacterial cell surface receptors. Entelli-02 exhibits 88% host coverage against The Alfred Hospital's ECC isolate collection (n = 206), confirmed by plaque formation and reduced bacterial load in septicaemic mice by >99%. We produced this cocktail as a therapeutic-grade product, ready for clinical use. Entelli-02 represents a hospital-specific phage cocktail with frontline efficacy and on-demand availability.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"81 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133993","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}
Li-Feng Du, Wenyu Shi, Xiao-Ming Cui, Huimin Fan, Jia-Fu Jiang, Cai Bian, Run-Ze Ye, Qian Wang, Ming-Zhu Zhang, Ting-Ting Yuan, Luo-Yuan Xia, Xiang-Dong Ruan, Qiao-Cheng Chang, Chun-Hong Du, Teng-Cheng Que, Xin Wang, Xiao-Hu Han, Tian-Ci Yang, Bao-Gui Jiang, Jian-Ying Chen, Xiao-Run Wang, Liang-Fei Tan, Yi-Wen Liu, Liang-Li Deng, Yan Liu, Yan Zhu, Yu-Sheng Pan, Ning Wang, Zhe-Tao Lin, Lian-Feng Li, Cheng Li, Shi-Jing Shen, Ya-Ting Liu, Di Tian, Xiao-Yu Han, Juan Wang, Yi-Fei Wang, Wan-Ying Gao, Yu-Yu Li, Tao Xiong, Tian-Hong Wang, Xiao-Yu Shi, Dai-Yun Zhu, Jin-Guo Zhu, Chong-Cai Wang, Wen-Qiang Shi, Lin Zhan, Zhi-Hong Liu, Dan Feng, Lin Zhao, Yi Sun, Tick Genome and Microbiome Consortium (TIGMIC), Jinfeng Wang, Na Jia, Fangqing Zhao, Wu-Chun Cao
{"title":"Genome-resolved metagenomics reveals microbiome diversity across 48 tick species","authors":"Li-Feng Du, Wenyu Shi, Xiao-Ming Cui, Huimin Fan, Jia-Fu Jiang, Cai Bian, Run-Ze Ye, Qian Wang, Ming-Zhu Zhang, Ting-Ting Yuan, Luo-Yuan Xia, Xiang-Dong Ruan, Qiao-Cheng Chang, Chun-Hong Du, Teng-Cheng Que, Xin Wang, Xiao-Hu Han, Tian-Ci Yang, Bao-Gui Jiang, Jian-Ying Chen, Xiao-Run Wang, Liang-Fei Tan, Yi-Wen Liu, Liang-Li Deng, Yan Liu, Yan Zhu, Yu-Sheng Pan, Ning Wang, Zhe-Tao Lin, Lian-Feng Li, Cheng Li, Shi-Jing Shen, Ya-Ting Liu, Di Tian, Xiao-Yu Han, Juan Wang, Yi-Fei Wang, Wan-Ying Gao, Yu-Yu Li, Tao Xiong, Tian-Hong Wang, Xiao-Yu Shi, Dai-Yun Zhu, Jin-Guo Zhu, Chong-Cai Wang, Wen-Qiang Shi, Lin Zhan, Zhi-Hong Liu, Dan Feng, Lin Zhao, Yi Sun, Tick Genome and Microbiome Consortium (TIGMIC), Jinfeng Wang, Na Jia, Fangqing Zhao, Wu-Chun Cao","doi":"10.1038/s41564-025-02119-z","DOIUrl":"10.1038/s41564-025-02119-z","url":null,"abstract":"Ticks are arthropod vectors capable of transmitting a wide spectrum of pathogens affecting humans and animals. However, we have relatively limited information of their genomic characteristics and the diversity of associated microbiomes. Here we used long- and short-read sequencing on 1,479 samples from 48 tick species across eight genera from China to determine their genome and associated pathogens and microbiome. Through de novo assembly, we reconstructed 7,783 bacterial genomes representing 1,373 bacterial species, of which, 712 genomes represented 32 potentially pathogenic species. Computational analysis found nutritional endosymbionts to be prevalent and highly specific to tick genera. The microbiome genome-wide association study revealed host genetic variants linked to pathogen diversity, abundance and key biological pathways essential to tick biology, including blood-feeding and pathogen invasion. These findings provide a resource for studying the host–microbe interactions within ticks, paving the way for strategies to control tick populations and tick-borne diseases. Sequencing the genome and microbiome of about 1,500 tick samples from regions across China revealed host–microbe associations in ticks that could have implications for controlling ticks and tick-borne diseases.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2631-2645"},"PeriodicalIF":19.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02119-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127153","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":"Deep-mining the archaeal proteome for antibiotics","authors":"Rafael Laso-Pérez","doi":"10.1038/s41564-025-02098-1","DOIUrl":"10.1038/s41564-025-02098-1","url":null,"abstract":"A deep-learning algorithm unravels a collection of archaeasins, peptides from the archaeal proteome with potential antimicrobial activity and implications for the development of next-generation antibiotics","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2365-2366"},"PeriodicalIF":19.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127154","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}
Shouheng Jin, Xing He, Zheyu Wang, Tao Zhou, Jun Wang, Guihong Pan, Yin Zhang, Ling Ma, Shuai Yang, Liqiu Wang, Yaoxing Wu, Yilin Zou, Nan Qi, Jun Cui
{"title":"Oxaloacetate sensing promotes innate immune antiviral defence against influenza virus infection","authors":"Shouheng Jin, Xing He, Zheyu Wang, Tao Zhou, Jun Wang, Guihong Pan, Yin Zhang, Ling Ma, Shuai Yang, Liqiu Wang, Yaoxing Wu, Yilin Zou, Nan Qi, Jun Cui","doi":"10.1038/s41564-025-02107-3","DOIUrl":"10.1038/s41564-025-02107-3","url":null,"abstract":"Metabolic pathways determine cellular fate and function; however, the exact roles of metabolites in host defence against influenza virus remain undefined. Here we employed pharmacological inhibition and metabolomics analysis to show that the metabolic pathways of oxaloacetate (OAA) are integrated with antiviral responses to influenza virus. Cytosolic malate dehydrogenase 1 senses intracellular OAA to undergo dimerization and functions as a scaffold to recruit the transcription factor ETS2 for phosphorylation by the kinase TAOK1 at serine 313. The phosphorylated ETS2 translocates into the nucleus and supports optimal expression of TBK1, an indispensable activator of type I interferon responses. OAA supplementation provides a broad-spectrum antiviral ability, and OAA deficiency caused by Acly genetic ablation decreases antiviral immunity and renders mice more susceptible to lethal H1N1 virus infection. Our results uncover a signalling pathway through cellular OAA sensing that links metabolism and innate immunity to coordinate defence against viral challenge. Oxaloacetate is sensed by MDH1, which primes innate immune antiviral defence against influenza virus infection, thus resulting in the activation of ETS2 to promote TBK1-centred type I interferon signalling.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2521-2536"},"PeriodicalIF":19.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117053","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}
Guoxiu Xiang, Yanan Wang, Kaiji Ni, Huoqing Luo, Qian Liu, Yan Song, Ping Miao, Lei He, Ying Jian, Ziyu Yang, Tianchi Chen, Ke Xu, Xia Sun, Zhen Shen, Chenfeng Ji, Na Zhao, Mengxin He, Yan Pan, Yanli Luo, Ji Hu, Michael Otto, Min Li
{"title":"Nasal Staphylococcus aureus carriage promotes depressive behaviour in mice via sex hormone degradation","authors":"Guoxiu Xiang, Yanan Wang, Kaiji Ni, Huoqing Luo, Qian Liu, Yan Song, Ping Miao, Lei He, Ying Jian, Ziyu Yang, Tianchi Chen, Ke Xu, Xia Sun, Zhen Shen, Chenfeng Ji, Na Zhao, Mengxin He, Yan Pan, Yanli Luo, Ji Hu, Michael Otto, Min Li","doi":"10.1038/s41564-025-02120-6","DOIUrl":"10.1038/s41564-025-02120-6","url":null,"abstract":"The human microbiome has a pronounced impact on human physiology and behaviour. Despite its unique anatomical connection to the brain, the role of the nasal microbiome in neurological diseases is understudied. Here, using human data and experiments in mice, we show that nasal Staphylococcus aureus is linked to depression. Nasal microbiome analyses revealed a positive correlation between depression scores and S. aureus abundance among patients with depression and healthy controls. Metabolomics of the nasal cavity showed decreased sex hormones, estradiol and testosterone in patients with depression versus controls. Nasal microbiota transplants from patients reproduced depression-like behaviour in mice with differential abundance of S. aureus. Further homology and mutational analysis uncovered an S. aureus sex hormone-degrading enzyme, 17b-hydroxysteroid dehydrogenase (Hsd12), which degraded testosterone and estradiol in mice, leading to lower levels of dopamine and serotonin in the murine brain. These findings reveal a nasal commensal that influences depressive behaviour and provides insights into the nose–brain axis. Nasal colonization by Staphylococcus aureus is linked with depression in a human cohort and shown in a mouse model to cause decreased serotonin and dopamine in the brain.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2425-2440"},"PeriodicalIF":19.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02120-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117056","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}