Nature Microbiology最新文献

{"title":"Microbiota-derived 10-hydroxystearic acid activates PPARα to restore gut epithelial barrier integrity and enhance anti-retroviral therapy","authors":"Dylan Kramer, Clarissa Santos Rocha, Christopher A. Gaulke, Marie Nearing, Sumathi Sankaran-Walters, Ikaika Loque, Anugraha Kidigannappa, Eric Pham, Shuang Hu, Patrawin Wanakumjorn, Ramona Abbattista, Abhaya Dandekar, Roland Faller, Satya Dandekar","doi":"10.1038/s41564-026-02433-0","DOIUrl":"10.1038/s41564-026-02433-0","url":null,"abstract":"HIV infection disrupts gut epithelial barrier integrity and mucosal immunity, driving chronic inflammation and disease progression which are not fully resolved despite anti-retroviral therapy. Here we identify the microbiota-derived octadecanoid-hydroxy-fatty-acid metabolite 10-hydroxystearic acid (10-HSA), produced by Lactiplantibacillus plantarum, as a key mediator of gut epithelial barrier repair in human intestinal epithelial cells in vitro, ex vivo and in the non-human primate model of HIV/AIDS. X-ray crystallography and transcriptomics combined with functional analyses revealed that 10-HSA directly binds PPARα, inducing lipid metabolism, mitochondrial regeneration and subsequent epigenetic histone crotonylation, thereby promoting gut epithelial renewal. Co-administration of 10-HSA with anti-retroviral therapy in SIV-infected macaques accelerated viral suppression, resolved systemic inflammation, repaired gut epithelial integrity and recovered the gut microbiota. These findings identify a microbiota-derived lipid metabolite–PPARα–histone crotonylation axis that activates gut epithelial regeneration. This study defines a host–microbiome metabolic pathway that restores epithelial–immune homeostasis and enhances the efficacy of anti-retroviral therapy. Lactiplantibacillus plantarum-derived fatty-acid metabolite, 10-hydroxystearic acid, interacts directly with PPARα to alter histone crotonylation and the transcriptional landscape which leads to gut barrier functional repair and enhanced viral suppression in non-human primate models when combined with anti-retroviral therapy.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2365-2383"},"PeriodicalIF":18.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02433-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612603","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":"Cell-autonomous immunity as an integrated immune network against bacterial and viral pathogens","authors":"Lorena Martín-González, Bruno Ramos, Yizhou Huang, Teresa Thurston, Greg Towers, Damián Lobato-Márquez","doi":"10.1038/s41564-026-02428-x","DOIUrl":"10.1038/s41564-026-02428-x","url":null,"abstract":"All cells possess a diverse array of cell-autonomous immune responses that can detect and restrict infections by intracellular pathogens. These intrinsic responses (both passive and active) enable individual cells to autonomously block bacterial and viral invasion and replication. Epithelial and endothelial cells act as a first line of defence, coordinating immune responses that preserve host barrier integrity. These cells can also mount specialized innate immune responses (many of which are triggered by antimicrobial cytokines, such as interferons) to limit the replication and motility of intracellular bacteria and viruses. To counteract these, bacteria and viruses have developed strategies to avoid or antagonize host defences, driving an evolutionary arms race that shapes every aspect of host–pathogen interactions. This Review provides an overview of current knowledge of cell-autonomous immunity against bacteria and viruses. We emphasize the factors underpinning host cell surveillance and restriction of cytosolic pathogens and mechanisms of immune evasion deployed by the invading microorganism. This Review summarizes the current knowledge about the cell-intrinsic factors that act against pathogenic bacteria and viruses and the immune evasion strategies that pathogens have to counteract cell-autonomous immunity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2098-2111"},"PeriodicalIF":18.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612814","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":"Gut microbiota restricts intestinal lipid uptake via modulation of bile phosphatidylcholine metabolism in mice","authors":"Sarah Brunner, Johannes Plagge, Maria Zimmermann-Kogadeeva, Marcus Höring, Gerhard Liebisch, Marijana Basic, Silvia Bolsega, Klaus-Peter Janssen, Emma Slack, Sophia von Gamm, Alina Viehof-Beckmann, Thomas Clavel, Michael Zimmermann, Joerg Heeren, Piero Giansanti, Anna S. Weiss, Sven Hermeling, Aline Dupont, Anna-Lena Ullrich, Florian Jokisch, Claudine Seeliger, Andre Bleich, Maria Hidrobo, Bärbel Stecher, Olivia I. Coleman, Claudia Moresi, Giorgia Greter, Markus Arnoldini, Josef Scheiber, Silke Matysik, Martin Klingenspor, Bernhard Küster, Dirk Haller, Ralph Burkhardt, Folkert Kuipers, Josef Ecker","doi":"10.1038/s41564-026-02434-z","DOIUrl":"10.1038/s41564-026-02434-z","url":null,"abstract":"The gut microbiota influences host metabolism, but the mechanisms of lipid uptake from food remain mysterious. Here we used stable isotope-labelled tracers in gnotobiotic mouse models, which revealed that host uptake of dietary lipids depends on microbial colonization. Systemic lipid metabolism modelling predicted that the gut microbiota restricts intestinal lipid absorption, and labelled lipid administration verified that the gut contents of microbiota-colonized mice contained up to 12-fold more lipids than those of germ-free animals. A combination of lipidomics and proteomics showed that gut microbes trigger Myd88 signalling, leading to a downregulation of hepatic Cyp7b1 activity and increased taurocholate production. Taurocholate stimulates phospholipase A1 activity in bile, causing the degradation of phosphatidylcholine that is essential for luminal micelle formation and lipid uptake. A diverse microbiome was associated with lower phosphatidylcholine content. This previously unrecognized host–gut microbiota interplay via enzymes in bile could provide future targets to modulate dietary lipid absorption. Lipidomics and proteomics in mice colonized with variable gut microbiota reveal an important role of gut microbes in restricting lipid uptake via triggering Myd88 signalling and the degradation of phosphatidylcholine in bile.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2349-2364"},"PeriodicalIF":18.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02434-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612604","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":"Phage hijacks host phosphorothioate DNA modification machinery to circumvent bacterial Ssp defences","authors":"Yifei Wang, Haoyi Yang, Lixu Jiang, Yashi Ge, Yuhang Zhong, Hui Chu, Kuo Zhang, Kadierya Kuerban, Yuan Nong, Haiyan Gao, Congrui Xu, Xiaoyu Li, Shi Chen, Lianrong Wang","doi":"10.1038/s41564-026-02387-3","DOIUrl":"10.1038/s41564-026-02387-3","url":null,"abstract":"The bacterial Ssp defence system discriminates self from non-self by introducing sequence-specific phosphorothioate (PT) modifications in host DNA (via SspABCD) and cleaving unmodified foreign DNA (via SspFGH or SspE). Here we report PptA, a phage-encoded [4Fe–4S] cluster-containing protein, which hijacks cognate host cysteine desulfurase IscS homologues to assemble a streamlined PT modification machinery. Integrated biochemical and structural data delineate a model for intermolecular sulfur transfer within the IscS–PptA complex. Upon infection, robust expression of PptA, not merely its presence, drives sufficient PT incorporation into the phage genome, enabling molecular mimicry of host PT patterns. By masquerading as ‘self’, the modified phage DNA evades recognition and cleavage by SspFGH/SspE. Notably, PptA can reprogramme the Ssp-sensitive λ phage into an immune-evasive variant. These results reveal a co-evolutionary strategy used by phages to overcome PT-based bacterial immunity and provide a foundation for engineering therapeutic phages that bypass this widespread defence system. The phage-encoded protein PptA enables its DNA to masquerade as the host and evade cleavage, providing a potential foundation for engineering therapeutic phages that could bypass this widespread defence system.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2187-2200"},"PeriodicalIF":18.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612605","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":"Unique adaptations in sulfatases underpin colonic mucin degradation by Akkermansia muciniphila","authors":"Debajit Dey, Naba D. Salman, Charles W. E. Tomlinson, Chunsheng Jin, Grete Raba, Sadie R. Schaus, Marcus Nilsson, Zak McIver, Reyme Herman, Adam Simpkin, Matthew Davy, Daniel J. Rigden, Mirjam Czjzek, Dominic P. Byrne, Mihai Oltean, Alexander Case, Christoph G. Baumann, Gareth S. A. Wright, Sjoerd van der Post, Edwin A. Yates, Eric C. Martens, Lauren Davey, Ana S. Luis, Alan Cartmell","doi":"10.1038/s41564-026-02424-1","DOIUrl":"10.1038/s41564-026-02424-1","url":null,"abstract":"Excessive foraging of colonic mucin glycans by gut bacteria is associated with diseases such as inflammatory bowel disease. Although Akkermansia muciniphila is an important mucin degrader, the role of carbohydrate sulfatases that facilitate digestion of these heavily sulfated glycans remains unclear. Combining in vitro digestion assays, proteomics and structural biology, we show that A. muciniphila sulfatases, such as Amuc1755 and Amuc0953, have rare adaptations targeted towards known sulfated mucin structures. They show larger degrees of modularity, including a previously unknown mucin-binding domain. When grown on colonic mucin substrates, glycoproteins of reduced size were important for the growth of A. muciniphila. Further mutational analysis and localization studies revealed that desulfation of N-acetyl-d-glucosamine was periplasmic, while desulfation of d-galactose occurred extracellularly and in the periplasm. These data improve our understanding of contexts for the positive health correlations of A. muciniphila while metabolizing colonic mucin as its sole carbon source. Structural and biochemical follow-up of a serendipitous discovery reveals that Akkermansia muciniphila carbohydrate sulfatases are uniquely adapted to digest colonic mucins in collaboration with other members of gut microbiota.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2525-2542"},"PeriodicalIF":18.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02424-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605486","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":"Antiviral GHP-88310 blocks contact-mediated and airborne transmission in a ferret model of measles-like disease","authors":"Carolin M. Lieber, Josef D. Wolf, Claire E. Ruckel, Lauren A. Harrison, Richard K. Plemper","doi":"10.1038/s41564-026-02419-y","DOIUrl":"10.1038/s41564-026-02419-y","url":null,"abstract":"The 2025/2026 measles resurgence in North America highlighted that antivirals may be valuable in protecting child health because of mounting vaccination hesitancy. The drug candidate GHP-88310 is an orally efficacious broad-spectrum orthoparamyxovirus polymerase inhibitor, but its effect on viral transmission is unclear. Here we used canine distemper virus, which causes measles-like disease in ferrets, and established direct-contact and airborne canine distemper virus transmission models to examine pharmacological suppression of virus spread. Prophylactic GHP-88310 administration alleviated clinical signs of direct contacts and all sentinels survived. Pre- and post-exposure prophylactic GHP-88310 given twice daily to air contacts prevented transmission. Once-daily prophylactic administration mediated complete survival with all air contacts undergoing seroconversion. Therapeutic treatment of air contacts mitigated clinical signs, and animals survived, whereas all vehicle-treated air contacts succumbed. Therapeutic treatment of infected source animals shortened the contagious phase by 5 days. These results establish conceptual proof that GHP-88310 can suppress social contact transmission. Therapeutic treatment of sources promises epidemiological gain in addition to therapeutic benefit. Antiviral candidate GHP-88310 provides therapeutic benefit against measles-like disease and protects against productive direct-contact and airborne viral transmission when used for pre- and post-exposure prophylaxis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2505-2514"},"PeriodicalIF":18.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02419-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584962","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":"Ebola virus persistence and the hidden cost of immune privilege","authors":"Amal Fahmi, Isabel Schultz-Pernice, Marco P. Alves","doi":"10.1038/s41564-026-02432-1","DOIUrl":"10.1038/s41564-026-02432-1","url":null,"abstract":"Human brain organoids reveal how Ebola virus establishes persistent infection within the immune-privileged environment of the central nervous system.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2080-2081"},"PeriodicalIF":18.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02432-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579157","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":"Within-patient gene transfer between transiently and chronically infecting bacteria causes extreme antibiotic resistance during lung infections","authors":"Sardar Karash, Hannah L. Betts, Matthew C. Radey, Samuel Lee, Sarah J. Morgan, Barbara J. Waddell, Sara Klee, Beth A. Traxler, Michael D. Parkins, Rafael E. Hernandez, Alison F. Feder, Colin Manoil, Pradeep K. Singh","doi":"10.1038/s41564-026-02414-3","DOIUrl":"10.1038/s41564-026-02414-3","url":null,"abstract":"Antibiotic resistance arising during infections is generally thought to be due to mutations in pathogen genomes. Here we studied Pseudomonas aeruginosa and Achromobacter collected from people with cystic fibrosis and non-cystic fibrosis bronchiectasis that suddenly developed 10,000-fold increases in tobramycin resistance after tobramycin treatment was initiated. Genomic analysis showed that resistance did not arise from mutation accumulation or strain displacement. Instead, it occurred because plasmid-borne resistance genes were transferred to the previously sensitive pathogens inside patients’ lungs. In some cases, we identified the bacteria that carried plasmids into patients’ lungs and they were species capable of environmental growth like Pseudomonas putida. The most commonly transferred gene was an aac(3) aminoglycoside N-acetyltransferase (aac(3)-IIId), not previously associated with clinical resistance. Further analysis suggested that this gene was mobilized from environmental bacteria by a transposon and incorporated into transmissible plasmids. This work shows that gene transfer between transiently and chronically infecting bacteria can produce sudden and large increases in antibiotic resistance during human infections. Antibiotic resistance gene acquisition by Pseudomonas aeruginosa and Achromobacter from transiently infecting bacteria drives rapid and extreme resistance to tobramycin during chronic lung infection within patients.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2321-2335"},"PeriodicalIF":18.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02414-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579187","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":"Groundwater microbial communities across the terrestrial subsurface","authors":"Kirsten Küsel, Mark Dopson","doi":"10.1038/s41564-026-02427-y","DOIUrl":"10.1038/s41564-026-02427-y","url":null,"abstract":"The terrestrial subsurface hosts one of Earth’s largest biomes, with groundwater systems representing major habitats for microbial life. In these environments, microbes persist under energy scarcity caused by the absence of photosynthesis, physical isolation and slow geochemical turnover, but the ecological principles underpinning their survival are poorly understood. Here we propose a framework of ‘microbial frugality’ to describe how evolutionary and physiological traits enable life to persist near the energetic minimum in groundwater. Key traits include low replication rates, genome streamlining, metabolic versatility and dependencies, and a standby metabolism that primes cells for rapid response to transient nutrient inputs. Central to this lifestyle is the necromass pump, the continual recycling of microbial biomass that creates an internally generated carbon reservoir sustaining long-term activity. Together, these traits collectively enable persistence across groundwater ecosystems and mirror principles known from the marine deep biosphere, suggesting convergent solutions to extreme oligotrophy. The efficiency, interdependence and necromass recycling associated with microbial frugality highlight the unique role of groundwater microbes in global biogeochemical cycles. Here the authors propose the concept of ‘microbial frugality’ as an evolutionary outcome of life under the chronic energy limitation of the subsurface and a way to understand Earth’s hidden biogeochemical engine.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2088-2097"},"PeriodicalIF":18.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549936","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":"Clarifying objectives to strengthen wastewater-based AMR surveillance","authors":"D. G. Joakim Larsson, Carl-Fredrik Flach, Ramanan Laxminarayan","doi":"10.1038/s41564-026-02429-w","DOIUrl":"10.1038/s41564-026-02429-w","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2078-2079"},"PeriodicalIF":18.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549925","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}