Cody Martin, Joanne B. Emerson, Simon Roux, Karthik Anantharaman
{"title":"A call for caution in the biological interpretation of viral auxiliary metabolic genes","authors":"Cody Martin, Joanne B. Emerson, Simon Roux, Karthik Anantharaman","doi":"10.1038/s41564-025-02095-4","DOIUrl":"10.1038/s41564-025-02095-4","url":null,"abstract":"Virus-encoded auxiliary metabolic genes (AMGs) are non-essential genes that increase viral fitness by maintaining or manipulating host metabolism during infection. AMGs are intriguing from an evolutionary perspective, as most viral genomes are highly compact and have limited coding capacity for accessory genes. Advances in viral (meta)genomics have expanded the detection of putative AMGs from viruses in diverse environments. However, this has also led to many instances of misannotation due to the limitations of annotation tools, resulting in misinterpretations about the roles of some viral genes. Here, we highlight studies that support claims about AMGs with more than just function predictions for guidance on best practices. We then propose the adoption of an expanded, inclusive view of all genes auxiliary to core viral functions with the term ‘auxiliary viral genes’ (AVGs), alongside an associated eco-evolutionary framework for considering the types of analyses that can better support claims made about AVGs. This Perspective discusses virus-encoded auxiliary metabolic genes and provides a framework for the biological interpretation of these genes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2122-2129"},"PeriodicalIF":19.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905914","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}
Arianna I. Krinos, Daniel Muratore, Meriel J. Bittner, Preston Akenga, Leslie Wallace Auerbach, Michael Dills, Emile Faure, Edgart Flores, Naomi M. Levine, Thiago Monteiro, Camille Richon, Benjamin S. Twining
{"title":"A call for early-career teams in interdisciplinary microbiology research","authors":"Arianna I. Krinos, Daniel Muratore, Meriel J. Bittner, Preston Akenga, Leslie Wallace Auerbach, Michael Dills, Emile Faure, Edgart Flores, Naomi M. Levine, Thiago Monteiro, Camille Richon, Benjamin S. Twining","doi":"10.1038/s41564-025-02097-2","DOIUrl":"10.1038/s41564-025-02097-2","url":null,"abstract":"Early-career researchers play an integral role in building and maintaining interdisciplinary microbiological research.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2097-2099"},"PeriodicalIF":19.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900369","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":"Collectively charting the landscape of antifungal and fungicide resistance","authors":"","doi":"10.1038/s41564-025-02104-6","DOIUrl":"10.1038/s41564-025-02104-6","url":null,"abstract":"Better knowledge of which fungal mutations give rise to antimicrobial resistance and by which mechanisms is key to improving treatment strategies and drug development. We assembled a comprehensive dataset of drug resistance mutations in fungal genomes and used it to uncover their diversity, conservation across species, impact on protein functions and potential for cross-resistance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2109-2110"},"PeriodicalIF":19.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900368","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":"Mycoviruses steer fungal fitness","authors":"Laura C. Echeverri Tirado, Amariliz Rivera","doi":"10.1038/s41564-025-02100-w","DOIUrl":"10.1038/s41564-025-02100-w","url":null,"abstract":"A mycovirus drives the fitness of the lung-infecting fungus Aspergillus fumigatus under stress, helping it to survive within immune cells, and thus shaping its pathogenesis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2106-2108"},"PeriodicalIF":19.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900125","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}
Diana M. Battaglia, Claire E. Post, Wenbo Yao, Angela Wahl, Lisa E. Gralinski, Hongwei Liu, Hong Dang, Victoria J. Madden, Kristen K. White, Sarah R. Leist, Kenneth H. Dinnion III, Gabriela De la Cruz, Bentley R. Midkiff, Heather M. Froggatt, Kendra Gully, Mark Zweigart, J. Rachel Reader, Katherine J. Olstad, Jeffrey I. Everitt, Koen K. A. Van Rompay, Kristina De Paris, Eniko Sajti, Raymond J. Pickles, Edward P. Browne, Corbin D. Jones, Richard C. Boucher Jr, Ralph S. Baric, J. Victor Garcia
{"title":"SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation","authors":"Diana M. Battaglia, Claire E. Post, Wenbo Yao, Angela Wahl, Lisa E. Gralinski, Hongwei Liu, Hong Dang, Victoria J. Madden, Kristen K. White, Sarah R. Leist, Kenneth H. Dinnion III, Gabriela De la Cruz, Bentley R. Midkiff, Heather M. Froggatt, Kendra Gully, Mark Zweigart, J. Rachel Reader, Katherine J. Olstad, Jeffrey I. Everitt, Koen K. A. Van Rompay, Kristina De Paris, Eniko Sajti, Raymond J. Pickles, Edward P. Browne, Corbin D. Jones, Richard C. Boucher Jr, Ralph S. Baric, J. Victor Garcia","doi":"10.1038/s41564-025-02090-9","DOIUrl":"10.1038/s41564-025-02090-9","url":null,"abstract":"COVID-19 and long COVID are characterized by a dysregulated immune response. However, the role of macrophages during viral infection is poorly defined. Here we demonstrate that SARS-CoV-2 infection results in increased macrophage numbers and extensive formation of enlarged lipid-laden macrophages or foam cells using humanized mice, rhesus macaques and post-mortem human lung tissue. Notably, infection by other coronaviruses tested, SARS-CoV-1, MERS-CoV and two bat coronaviruses (SHC014-CoV or WIV1-CoV), did not result in macrophage proliferation or foam cell formation. Foam cells in SARS-CoV-2-infected human lung tissue display a pro-fibrotic and pro-thrombotic phenotype as they are enriched for genes associated with platelet activation and aggregation, as well as extracellular matrix organization and collagen synthesis. After viral clearance, macrophage numbers remain elevated, and lung fibrosis and thrombi persist. Importantly, we show that pre-exposure prophylaxis or early treatment with a SARS-CoV-2 antiviral, EIDD-2801, prevents increases in macrophage cell numbers and foam cell formation, and reduces fibrosis markers. These observations highlight the contribution of macrophages to lung inflammation and tissue injury leading to the pulmonary fibrosis observed in COVID-19 patients. SARS-CoV-2 infection can lead to sustained increased macrophage numbers and formation of enlarged lipid-laden macrophages after viral clearance. This can be prevented with antiviral treatment in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2616-2630"},"PeriodicalIF":19.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900126","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":"Amyloids in bacterial antiphage defence","authors":"Ali Nabhani, Benjamin R. Morehouse","doi":"10.1038/s41564-025-02102-8","DOIUrl":"10.1038/s41564-025-02102-8","url":null,"abstract":"Bacterial prions form amyloids in response to phage infection and induce cell death to prevent viral replication, similar to the processes in fungi and across the tree of life.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2104-2105"},"PeriodicalIF":19.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900130","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}
Eunsoo Do, C. Joel McManus, Robert Zarnowski, Manning Y. Huang, Katharina Goerlich, David R. Andes, Aaron P. Mitchell
{"title":"Ume6 protein complexes connect morphogenesis, adherence and hypoxic genes to shape Candida albicans biofilm architecture","authors":"Eunsoo Do, C. Joel McManus, Robert Zarnowski, Manning Y. Huang, Katharina Goerlich, David R. Andes, Aaron P. Mitchell","doi":"10.1038/s41564-025-02094-5","DOIUrl":"10.1038/s41564-025-02094-5","url":null,"abstract":"Biofilms of the fungal pathogen Candida albicans can form on implanted medical devices and contribute to fungal virulence and are recalcitrant to antifungal therapy. The transcription factor Ume6 directs hyphal cell elongation and thus promotes biofilm formation in C. albicans. However, how exactly this key biofilm and virulence regulator functions has remained unclear. Here RNA sequencing and chromatin immunoprecipitation with sequencing data show that Ume6 binds to and activates multiple biofilm-relevant genes. Ume6-associated sequence motifs correspond to binding sites for biofilm master regulators Efg1 and Ndt80, and hypoxic response regulator Upc2. Co-immunoprecipitation assays show the existence of Ume6–Efg1, Ume6–Ndt80 and Ume6–Upc2 protein complexes. Promoter binding of Ume6 is partially dependent upon Efg1, Ndt80 or Upc2, as is Ume6 target gene activation, thus indicating that the protein complexes function to drive Ume6–target gene interaction. Ume6 therefore acts as a bridge that connects the hyphal morphogenesis and adherence genes that shape biofilm architecture and the hypoxic response genes required for growth in the low-oxygen biofilm environment. These findings are vital for our understanding of the pathobiology of C. albicans and could open the way to new treatment options. Complexes of the transcription factor Ume6 bridge morphogenesis, adherence and hypoxic genes that determine biofilm architecture in the human fungal pathogen Candida albicans.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2231-2244"},"PeriodicalIF":19.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02094-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900131","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":"An atlas for tick immune cells","authors":"Cameron G. Coyle, Dana K. Shaw","doi":"10.1038/s41564-025-02092-7","DOIUrl":"10.1038/s41564-025-02092-7","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2100-2101"},"PeriodicalIF":19.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900363","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}
Carlotta Penzo, Ilayda Özel, Moreno Martinovic, Maja Kuzman, Dunja Glavas, Mia Stanic, Thomas Reichenbach, Thorsten G. Müller, Mona Rheinberger, Negar Godarzi, Delphine Lapaillerie, Bruno Srezovic, Maria Chiara dell’Oca, Laura C. Lange, Lopamudra Sadhu, Ines J. de Castro, Iart Luca Shytaj, Mattia Forcato, Vibor Laketa, Silvio Bicciato, Kristian Vlahovicek, Oliver T. Fackler, Bojana Lucic, Vlad Pena, Hans-Georg Kräusslich, Vincent Parissi, Marina Lusic
{"title":"Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions","authors":"Carlotta Penzo, Ilayda Özel, Moreno Martinovic, Maja Kuzman, Dunja Glavas, Mia Stanic, Thomas Reichenbach, Thorsten G. Müller, Mona Rheinberger, Negar Godarzi, Delphine Lapaillerie, Bruno Srezovic, Maria Chiara dell’Oca, Laura C. Lange, Lopamudra Sadhu, Ines J. de Castro, Iart Luca Shytaj, Mattia Forcato, Vibor Laketa, Silvio Bicciato, Kristian Vlahovicek, Oliver T. Fackler, Bojana Lucic, Vlad Pena, Hans-Georg Kräusslich, Vincent Parissi, Marina Lusic","doi":"10.1038/s41564-025-02089-2","DOIUrl":"10.1038/s41564-025-02089-2","url":null,"abstract":"HIV-1 integration into host chromosomes, essential for viral replication, is catalysed by viral integrase (IN). IN recurrently targets intronic regions of transcriptionally active genes, but a detailed understanding of this process is still unclear. Here, using ex vivo activated human primary CD4+T cells, we find that genomic RNA:DNA hybrids (R-loops) preferentially map to intronic regions of active genes that are typical HIV-1 integration sites. IN binds R-loops and their resolution enhances viral integration in vitro. We identify Aquarius (AQR), the splicing RNA helicase of the pentameric intron binding complex (IBC), which associates with IN and show that its RNA:DNA helicase activity promotes integration into hybrid substrates in vitro. Knockout of AQR in primary CD4+ T cells impaired overall integration efficiency, while sequencing of remaining integrations mapped them to intergenic and R-loop distal regions. These findings may have important implications for HIV-1 latency and reactivation and may thus identify novel therapeutic targets. R-loops formed by RNA hybridization to DNA template strand during transcription influence HIV-1 integration into the CD4+ T cell genome. The unwinding of R-loops by splicing helicase Aquarius facilitates integration into speckle-associated domains.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2306-2322"},"PeriodicalIF":19.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900362","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}
Linsen Pei, Yujia Xian, Xiaodan Yan, Charley Schaefer, Aisha H. Syeda, Jamieson A. L. Howard, Wei Zhang, Hebin Liao, Fan Bai, Mark C. Leake, Yingying Pu
{"title":"Aggresomes protect mRNA under stress in Escherichia coli","authors":"Linsen Pei, Yujia Xian, Xiaodan Yan, Charley Schaefer, Aisha H. Syeda, Jamieson A. L. Howard, Wei Zhang, Hebin Liao, Fan Bai, Mark C. Leake, Yingying Pu","doi":"10.1038/s41564-025-02086-5","DOIUrl":"10.1038/s41564-025-02086-5","url":null,"abstract":"Membraneless droplets formed through liquid–liquid phase separation of ribonucleoprotein particles contribute to mRNA storage in eukaryotic cells. How such aggresomes contribute to mRNA dynamics under stress and their functional role are less understood in bacteria. Here we used multiple approaches including live-cell imaging, polymer physics modelling and transcriptomics to show that prolonged stress leading to ATP depletion in Escherichia coli results in increased aggresome formation, compaction and selective mRNA enrichment within these aggresomes. Longer transcripts accumulate more in aggresomes than in the cytosol. Mass spectrometry and mutagenesis studies showed that mRNA ribonucleases are excluded from aggresomes due to electrostatic repulsion arising from their negative surface charges. Experiments with fluorescent reporters and disruption of aggresome formation showed that mRNA storage within aggresomes promoted rapid translation reactivation and is associated with reduced lag phases during growth after stress removal. Our findings suggest that mRNA storage within aggresomes confers an advantage for bacterial survival and recovery from stress. Ribonucleoprotein aggresomes exclude ribonucleases and protect mRNA to promote rapid translation reactivation and cellular recovery after stress alleviation in Escherichia coli.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2323-2337"},"PeriodicalIF":19.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883237","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}