Andrew A. Verdegaal, Joonseok Oh, Bahar Javdan, Ruojun Wang, Qihao Wu, Timothy R. W. Wang, Jaime A. González-Hernández, Mohamed S. Donia, Jason M. Crawford, Andrew L. Goodman
{"title":"A drug–microbiome–drug interaction impacts co-prescribed medications for Parkinson’s disease","authors":"Andrew A. Verdegaal, Joonseok Oh, Bahar Javdan, Ruojun Wang, Qihao Wu, Timothy R. W. Wang, Jaime A. González-Hernández, Mohamed S. Donia, Jason M. Crawford, Andrew L. Goodman","doi":"10.1038/s41564-026-02299-2","DOIUrl":"https://doi.org/10.1038/s41564-026-02299-2","url":null,"abstract":"Simultaneous prescription of multiple drugs is widespread in medicine. Although the gut microbiome is implicated in drug responses, its role in mediating drug–drug interactions is unexplored. Catechol-O-methyltransferase inhibitors (COMT-I), a class of drugs used alongside levodopa (L-DOPA) to treat Parkinson’s disease symptoms, can alter microbiome composition in patients. Here we characterize the antibiotic properties of COMT-I drugs in vitro, ex vivo and in vivo and dissect how these interactions alter microbiome-mediated L-DOPA metabolism in vitro and ex vivo. Notably, in vitro iron availability determines COMT-I antibiotic activity at multiple levels: extracellular iron can drive non-enzymatic inactivation of COMT-I, rescuing COMT-I-mediated bacterial iron starvation responses. However, limitation of intracellular iron can protect sensitive bacteria from COMT-I antibiotic activity. Co-administration of COMT-I and L-DOPA to human faecal microbial communities ex vivo results in COMT-I-dependent alterations to L-DOPA metabolism in an individual-specific manner. These studies highlight a role for the gut microbiome in mediating drug–drug interactions and identify microbial features that could predict individual responses to co-prescribed drugs.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"16 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619936","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}
Venkadesaperumal Gopu, Saurabh Bhattacharya, Michal Bejerano-Sagie, Mei Zhuang, Yuval Nevo, Oren Yakovian, Bushra Shraiteh, Miriam Ravins, Manas Kumar Guria, Tamar Kahan, Boris Maček, Ilan Rosenshine, Sigal Ben-Yehuda
{"title":"A family of endonucleases blocks nanotube-mediated plasmid exchange","authors":"Venkadesaperumal Gopu, Saurabh Bhattacharya, Michal Bejerano-Sagie, Mei Zhuang, Yuval Nevo, Oren Yakovian, Bushra Shraiteh, Miriam Ravins, Manas Kumar Guria, Tamar Kahan, Boris Maček, Ilan Rosenshine, Sigal Ben-Yehuda","doi":"10.1038/s41564-026-02293-8","DOIUrl":"10.1038/s41564-026-02293-8","url":null,"abstract":"Horizontal transfer of small non-conjugative plasmids is primarily attributed to transformation, transduction or comobilization with conjugative elements; however, transfer through intercellular membranous nanotube conduits can also occur. Here we show that nanotube-dependent plasmid exchange (NPex) operates bidirectionally between bacteria, enabling plasmid donation and, to a lesser extent, plasmid acquisition. We identified a Bacillus subtilis isolate, BSB1, deficient in NPex and show that a prophage-encoded factor, YokF, blocks plasmid transmission. YokF is an endonuclease that localizes to the membrane of donor bacteria, where it interacts with the nanotube component, FlhA, to impede plasmid transfer through DNA degradation. We further show that YokF provides an advantage to donor bacteria by restricting the sharing of beneficial plasmids with competing neighbouring cells. Bioinformatics and functional analyses revealed that YokF homologues are widespread across Gram-positive bacteria, representing a conserved family of gatekeepers that restrict plasmid flow via NPex. The YokF endonuclease provides a donor-controlled mechanism to limit plasmid transfer to recipient bacteria via nanotubes in Bacillus subtilis, with YokF functional homologues found across Gram-positive bacterial species.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"960-975"},"PeriodicalIF":19.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611809","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}
Vishnu Prasoodanan PK, Oleksandr M. Maistrenko, Anthony Fullam, Daniel R. Mende, Ece Kartal, Luis Pedro Coelho, Anja Spang, Peer Bork, Thomas S. B. Schmidt
{"title":"Unbinned contigs expand known diversity in the global microbiome","authors":"Vishnu Prasoodanan PK, Oleksandr M. Maistrenko, Anthony Fullam, Daniel R. Mende, Ece Kartal, Luis Pedro Coelho, Anja Spang, Peer Bork, Thomas S. B. Schmidt","doi":"10.1038/s41564-026-02314-6","DOIUrl":"https://doi.org/10.1038/s41564-026-02314-6","url":null,"abstract":"The ongoing census of microbial life is hampered by disparate sampling across Earth’s habitats, challenges in isolating uncultivated organisms, limited resolution in taxonomic marker gene amplicons and incomplete recovery of metagenome-assembled genomes. Here we quantify discoverable Bacterial and Archaeal diversity in a comprehensive, curated cross-habitat dataset of 92,187 publicly available metagenomes. Clustering 502 million sequences of 130 marker genes, we predict ~705,000 Bacterial and ~27,000 Archaeal species-level clades, the vast majority of which were hidden among unbinned contigs. We estimate that ten and 145 previously undescribed Archaeal and Bacterial phyla, respectively, are discoverable in this dataset. We identify soils and aquatic environments as hotspots of discoverable lineages, but predict that undescribed taxa remain abundant across all habitats. Finally, we show that prokaryotic diversity appears to arise within common evolutionary patterns, as clade size distributions follow power laws, consistently across the Tree of Life.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"27 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611811","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}
Kristen M. Zarrella, Ryan M. Sheridan, Brian C. Ware, Bennett J. Davenport, Mariana O. L. da Silva, Dariia Vyshenska, Aspen U. Martin, Nick A. May, Erin R. Fish, Daniela Weiskopf, Jay R. Hesselberth, Daniel N. Streblow, Alex L. Greninger, Thomas E. Morrison
{"title":"Chikungunya virus persists in joint-associated macrophages and promotes chronic disease in mice","authors":"Kristen M. Zarrella, Ryan M. Sheridan, Brian C. Ware, Bennett J. Davenport, Mariana O. L. da Silva, Dariia Vyshenska, Aspen U. Martin, Nick A. May, Erin R. Fish, Daniela Weiskopf, Jay R. Hesselberth, Daniel N. Streblow, Alex L. Greninger, Thomas E. Morrison","doi":"10.1038/s41564-026-02303-9","DOIUrl":"https://doi.org/10.1038/s41564-026-02303-9","url":null,"abstract":"Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus and Ross River virus, cause long-lasting musculoskeletal pain and inflammation. However, the mechanisms driving chronic disease remain unclear. Here, we used single-cell RNA sequencing, spatial transcriptomics and flow cytometry to investigate joint-associated tissues in alphavirus-infected mice at a late stage of infection. We identified an accumulation of inflammatory macrophages in joint-associated tissues with elevated expression of inflammatory markers. These cells harbour CHIKV RNA, suggesting ongoing viral replication during chronic disease. We also identified an accumulation of CD4+ T cells in these tissues expressing Ifng, and found that depletion of CD4+ T cells diminished major histocompatibility complex class II expression on joint macrophages, highlighting their potential role in inflammation. Treatment with a small molecule inhibitor of CHIKV replication during chronic disease reduced viral RNA and joint inflammation. Our data suggest that macrophages harbour replicating viral RNA and contribute to the sustained joint inflammation associated with chronic alphavirus disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"52 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585916","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":"Retraction Note: MAVS is a sensor of fumarate during antiviral immunity.","authors":"Yukun Min,Luke A J O'Neill","doi":"10.1038/s41564-026-02340-4","DOIUrl":"https://doi.org/10.1038/s41564-026-02340-4","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"99 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585407","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}
Frank X Ferrer-González,Katherine R Heal,Joshua S Sacks,Yarinet Romero-Maysonet,Anna H Finch,Laura T Carlson,Lisa S Y Coe,Zinka Bartolek,Claudia B Luthy,Moira P Gaffney,Sabine K Angier,Samantha E Flynn,Chiara I Bachmann Gómez,Jensen M L Dunn,Kenzie J Bay,Lia A Yamamoto,Matthew Z Tien,E Virginia Armbrust,Bryndan P Durham,Oscar A Sosa,Anitra E Ingalls
{"title":"Conserved pathway for homarine catabolism in environmental bacteria.","authors":"Frank X Ferrer-González,Katherine R Heal,Joshua S Sacks,Yarinet Romero-Maysonet,Anna H Finch,Laura T Carlson,Lisa S Y Coe,Zinka Bartolek,Claudia B Luthy,Moira P Gaffney,Sabine K Angier,Samantha E Flynn,Chiara I Bachmann Gómez,Jensen M L Dunn,Kenzie J Bay,Lia A Yamamoto,Matthew Z Tien,E Virginia Armbrust,Bryndan P Durham,Oscar A Sosa,Anitra E Ingalls","doi":"10.1038/s41564-026-02313-7","DOIUrl":"https://doi.org/10.1038/s41564-026-02313-7","url":null,"abstract":"Homarine (N-methylpicolinic acid) is a ubiquitous marine metabolite produced by phytoplankton and noted for its infochemical properties among marine animals, yet its microbial degradation pathways are uncharacterized. Here we identify a conserved operon (homABCDER) that mediates homarine catabolism in bacteria using comparative transcriptomics, mutagenesis and targeted knockouts. Phylogenetic and genomic analyses show that this operon is distributed across abundant bacterial clades, including coastal copiotrophs (for example, Rhodobacterales) and open-ocean oligotrophs (for example, SAR11, SAR116), and in genomes from non-marine environments. High-resolution mass spectrometry revealed N-methylglutamic acid and glutamic acid as key metabolic products of homarine in both model and natural systems, with N-methyl-glutamate dehydrogenase catalysing their conversion. Metatranscriptomics showed responsive and in situ expression of hom genes aligned with homarine availability. These findings uncover the genetic and metabolic basis of homarine degradation, establish its ecological relevance and highlight homarine as a versatile growth substrate that feeds into central metabolism via glutamic acid in diverse marine bacteria.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"34 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147578313","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}
Lianne I. M. Lansink, Htay Mon Aye, Leon Walther, Sophie Longmore, Madeleine Jones, Adam Dowle, João L. Reis-Cunha, Joana R. C. Faria
{"title":"Specialized RNA decay fine-tunes monogenic antigen expression in Trypanosoma brucei","authors":"Lianne I. M. Lansink, Htay Mon Aye, Leon Walther, Sophie Longmore, Madeleine Jones, Adam Dowle, João L. Reis-Cunha, Joana R. C. Faria","doi":"10.1038/s41564-026-02289-4","DOIUrl":"10.1038/s41564-026-02289-4","url":null,"abstract":"Antigenic variation is an immune evasion strategy used by pathogens, including Trypanosoma brucei. This parasite expresses a single variant surface glycoprotein (VSG) from a large genetic repertoire, which it periodically switches throughout an infection. VSGs are co-transcribed with expression-site-associated genes (ESAGs) within a specialized nuclear body, but there is substantial differential expression and the regulatory mechanisms remain unclear. Here we applied TurboID-mediated proximity labelling mass spectrometry to map the subnuclear expression-site body (ESB) post-transcriptional network. We identify and characterize three previously undescribed components: ESB-associated protein 1 (ESAP1) and ESB-specific proteins 2 and 3 (ESB2 and 3). These proteins form discreet subnuclear condensates that are developmentally regulated. ESB2 is an active RNA endonuclease that negatively regulates ESAG transcripts. Its recruitment depends on a hierarchy involving VEX2, ESAP1 and ESB3, a constant flux of active transcription and RNA processing, and its own nuclease activity. Overall, we uncover a molecular mechanism that fine-tunes expression of virulence genes through specialized RNA decay in T. brucei. To evade the immune system, Trypanosoma brucei relies on a specialized ‘expression site body’. Protein condensates within this nuclear compartment modulate expression of virulence genes via a targeted RNA decay mechanism.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"1080-1099"},"PeriodicalIF":19.4,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02289-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147578312","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}
Yongchao Xie, Gao Chen, Matthew J. Keller, Broquell M. Wong, Diana Ramirez, Cynthia M. Swift, Dana L. Carper, Paul E. Abraham, Andrew J. Stai, Robert L. Hettich, Amanda L. May, Shawn R. Campagna, Jessica A. LaFond, Jennifer L. Guelfo, Anita Thapalia, Trent A. Key, Frank E. Löffler
{"title":"Bacteria covalently incorporate polyfluoroalkyl carboxylates into membrane lipids","authors":"Yongchao Xie, Gao Chen, Matthew J. Keller, Broquell M. Wong, Diana Ramirez, Cynthia M. Swift, Dana L. Carper, Paul E. Abraham, Andrew J. Stai, Robert L. Hettich, Amanda L. May, Shawn R. Campagna, Jessica A. LaFond, Jennifer L. Guelfo, Anita Thapalia, Trent A. Key, Frank E. Löffler","doi":"10.1038/s41564-026-02301-x","DOIUrl":"10.1038/s41564-026-02301-x","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFASs), also known as forever chemicals, are global contaminants, but understanding of microbiota–PFAS interactions is limited. Here we show that bacteria covalently incorporate n:3 fluorotelomer carboxylates (FTCAs) into phosphatidylethanolamine and phosphatidylglycerol, two prominent components of bacterial lipid bilayers. Lipidomics of the soil bacterium Pseudomonas sp. strain 273 grown in the presence of 7:3 FTCA or 8:3 FTCA estimated that 7–12% of the bacterium’s glycerophospholipid pool contains the respective polyfluoroacyl chains. This covalent incorporation was observed in five other axenic bacterial cultures tested, including other Pseudomonas species, Escherichia coli and Enterococcus faecalis, albeit with lower incorporation percentages. Incorporation occurred over a broad concentration range, and n:3 FTCAs with varying chain length were covalently incorporated into membranes. Biotransformation of polyfluoroalkyl substances (also known as precursors) results in n:3 FTCA intermediates, which bacteria can covalently incorporate into their glycerophospholipid pools. We conclude that bacteria can form fluoromembranes when exposed to precursors and are a potential PFAS sink. Bacteria are able to covalently incorporate n:3 polyfluoroalkyl carboxylates into phosphatidylethanolamine and phosphatidylglycerol, two major components of bacterial lipid bilayers.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"929-939"},"PeriodicalIF":19.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147524394","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":"Aquatic virus transmission to humans","authors":"Fabian H. Leendertz, Stephanie Markert","doi":"10.1038/s41564-026-02306-6","DOIUrl":"10.1038/s41564-026-02306-6","url":null,"abstract":"A human eye disease seems to be linked to covert mortality nodavirus, a virus commonly found in aquatic animals. The findings suggest that zoonotic transmission to humans occurs through close contact.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"845-846"},"PeriodicalIF":19.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531155","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}