Nature Microbiology最新文献

{"title":"Antisense transcription reveals disease-associated adaptations in the human gut microbiome","authors":"Marie-Madlen Pust, Ahmed M. T. Mohamed, Martin Stražar, Aranzazu Arias-Rojas, Edward Cunningham-Oakes, Eric M. Brown, Amanda Bumber, Gleb Pishchany, Chenhao Li, Ashwin N. Ananthakrishnan, Alistair C. Darby, Hera Vlamakis, Damian R. Plichta, Ramnik J. Xavier","doi":"10.1038/s41564-026-02442-z","DOIUrl":"10.1038/s41564-026-02442-z","url":null,"abstract":"The gut microbiome is a dynamic ecosystem in which microorganisms constantly adjust their transcriptional programmes. Here we developed metastrand, a framework that integrates strand-aware metatranscriptomics and metagenomics to quantify mRNAs and antisense RNAs (asRNAs) in complex microbial communities at gene-level resolution. In inflammatory bowel disease (IBD), microbial asRNA programmes converged across patients during active disease, correlated with faecal metabolites and calprotectin levels and remained stable during persistent inflammation, highlighting their potential as biomarkers of inflammatory activity in the gut. These programmes involved antisense-to-sense transcriptional shifts at insertion sequence elements with functionally diverse passenger genes and preceded their detection at new genomic locations, linking asRNA dynamics to structural genome rearrangements and redistribution of adaptive functions under selective pressure. Similar dynamics were observed in a mouse model of colitis, oxidative stress in vitro and in patients with pathogen-confirmed gastroenteritis, establishing asRNAs as an important dimension of microbial adaptation in health and disease. Metastrand integrates strand-aware metatranscriptomic and metagenomic data to distinguish microbial sense from antisense transcription at gene-level resolution, and a use case study highlights the importance of antisense RNAs in understanding the microbial dynamics in inflammatory bowel disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2464-2477"},"PeriodicalIF":18.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707104","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":"Bacterial symbionts and the lightness of being a prokaryote","authors":"Silvia Bulgheresi","doi":"10.1038/s41564-026-02440-1","DOIUrl":"10.1038/s41564-026-02440-1","url":null,"abstract":"Silvia Bulgheresi muses on how studying bacterial symbionts of worms and mammals made her question whether the absence of a nucleus enables cellular freedom, potentiating architectural innovation and functional adaptation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2389-2390"},"PeriodicalIF":18.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707101","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":"Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV.","authors":"Jonah B Sacha, Tracy Ordonez, Shilpi Pandey, Gabriela Webb, Philip Barnette, Cleiton Pessoa, Matthew C Humkey, Jason Reed, Anden Morehead, Jennifer K Watanabe, Jodie L Usachenko, Shrivaas Vijayan, Altair Fazio, Heather Sidener, Anne D Lewis, Gabrielle Pastenkos, Sohita Ojha, Aaron Barber-Axthelm, Bella Swan, Rachele Bochart, John R Mascola, Amarendra Pegu, Emily J Fray, Rachael M Wolters, Janet D Siliciano, Robert F Siliciano, Scott G Hansen, Koen K A Van Rompay, Ann J Hessell, Nancy L Haigwood","doi":"10.1038/s41564-026-02444-x","DOIUrl":"10.1038/s41564-026-02444-x","url":null,"abstract":"<p><p>Lack of access to antiretroviral therapy (ART) leads to the transmission of human immunodeficiency virus in ~120,000 children annually, emphasizing the need for new strategies to prevent lifelong infection. Here in an infant rhesus macaque model of peripartum oral infection, we show that broadly neutralizing antibodies directed to the viral envelope protein were insufficient to prevent latent reservoir establishment, independent of daily ART. Blockade of the human immunodeficiency virus co-receptor CCR5 via the antibody leronlimab also failed to prevent reservoir establishment, but it significantly reduced reservoir seeding in lymphoid and gastrointestinal tissues. Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707254","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":"Antiviral defence is a conserved function of diverse bacterial DNA glycosylases","authors":"Landon J. Getz,&nbsp;Amy L. Qian,&nbsp;Y. Vivian Liu,&nbsp;Sam R. Fairburn,&nbsp;Mahnoor S. Butt,&nbsp;Yan-Jiun Lee,&nbsp;Peter R. Weigele,&nbsp;Karen L. Maxwell","doi":"10.1038/s41564-026-02441-0","DOIUrl":"10.1038/s41564-026-02441-0","url":null,"abstract":"Bacteria are frequently attacked by viruses, known as phages, and rely on diverse defence systems to survive. While phages can evade defences by covalently modifying their DNA, these non-canonical nucleobases create molecular signatures that bacteria can exploit. Here, using structure-guided discovery, we identified two widespread families of anti-phage DNA glycosylases, Dag1 and Dag2. Although DNA glycosylases are classically associated with DNA repair, Dag1 and Dag2 act as antiviral effectors that selectively target phages carrying modified guanine bases. Guided by the conserved glycosylase fold, we uncovered numerous defence-associated glycosylases that collectively form a diverse repertoire of enzymes targeting chemically modified phage DNA. We further identified a distinct glycosylase superfamily that protects against phages carrying modified thymidine bases. Together, these findings establish DNA glycosylases as a versatile class of bacterial immune proteins and highlight structure-guided discovery as a powerful strategy for uncovering hidden antiviral defences. DNA glycosylases, typically used for DNA repair, can also protect bacteria against phages that would otherwise evade host immunity by incorporating modified bases into their genomes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2589-2600"},"PeriodicalIF":18.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685332","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":"Genomic surveillance reveals co-occurrence of Plasmodium falciparum drug resistance variants across diverse transmission settings in Ethiopia","authors":"Alemayehu Letebo,&nbsp;Leen N. Vanheer,&nbsp;Mengst Engdaw,&nbsp;Legesse Alamerie Ejigu,&nbsp;Dawit Hailu Alemayehu,&nbsp;Jimma Dinsa Deressa,&nbsp;Bethlehem Adnew,&nbsp;Abaysew Ayele,&nbsp;Migbaru Keffale Bezabih,&nbsp;Mulugeta Demisse,&nbsp;Tamrayehu Seyoum,&nbsp;Meklit Shiferaw,&nbsp;Heven Sime,&nbsp;Atsbeha Gebreegziabxier Weldemariam,&nbsp;Amanuel Shimelash,&nbsp;Elias B. Tafa,&nbsp;Wakweya Chali,&nbsp;Lina Alemayehu,&nbsp;Fikregabrail Aberra Kassa,&nbsp;Ayalew Jejaw Zeleke,&nbsp;Tajudin Abdurhaman Hamza,&nbsp;Abel Beliyu Tamirat,&nbsp;Tadesse Misganaw,&nbsp;Alayu Bogale,&nbsp;Zufan Yiheyis Abriham,&nbsp;Yasin Nasir,&nbsp;Gutema Jebessa,&nbsp;Metmiku Yohannes,&nbsp;Betelhem Akililu Kebede,&nbsp;Matiwos Kidane Ayele,&nbsp;Melat Abdo,&nbsp;Getinet Habtamu,&nbsp;Addisu Gizat,&nbsp;Jody Phelan,&nbsp;Bryce Matlock,&nbsp;David A. Fidock,&nbsp;Susana Campino,&nbsp;Ashenafi Assefa,&nbsp;Cristian Koepfli,&nbsp;Fekadu Massebo,&nbsp;Fitsum G. Tadesse","doi":"10.1038/s41564-026-02420-5","DOIUrl":"10.1038/s41564-026-02420-5","url":null,"abstract":"The emergence of antimalarial drug resistance threatens malaria control and elimination efforts in Africa. Ethiopia, once a success story in case reduction, is now experiencing a resurgence. Here we examine key drug resistance genes (Pfmdr1, Pfcrt, Pfk13, Pfdhfr and Pfdhps) and mitochondrial genomes from 605 Plasmodium falciparum isolates collected across 15 districts in Ethiopia with varying transmission intensity and Plasmodium vivax co-endemicity. Although chloroquine was withdrawn for P. falciparum long ago, it remains the first-line treatment for P. vivax; this overlapping use may shape selection pressure in co-endemic settings that influences resistance markers to artemether–lumefantrine, the current first-line therapy for P. falciparum. A dominant PfMDR1 NFSND haplotype, associated with reduced lumefantrine susceptibility, was identified alongside near fixation of the chloroquine-resistant PfCRT CVIET haplotype in specific areas. Concerningly, PfK13 variants associated with partial artemisinin resistance, R622I (10%), A675V (1.7%) and P441L (1.1%), were expanding. Multilevel models demonstrated robust, independent associations of R622I with PfCRT CVIET and PfDHFR AICNI, while ecological predictors were weaker and less consistent. These findings highlight genetic co-occurrence of Pfcrt and Pfk13 mutations in P. vivax–P. falciparum co-endemic settings and can inform antimalarial policy in Ethiopia. Artemisinin partial resistance is expanding in Ethiopia and, together with a dominant lumefantrine-tolerant PfMDR1 haplotype and co-occurring Pfcrt and Pfk13 mutations, defines a complex multidrug-resistance landscape that may reflect overlapping treatment pressures in Plasmodium vivax and Plasmodium falciparum co-endemic settings.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2577-2588"},"PeriodicalIF":18.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02420-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679406","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":"IL-1 family signalling drives mucosal defence against systemic Candida albicans infection","authors":"James S. Griffiths,&nbsp;Alexander Kempf,&nbsp;Robert J. Pickering,&nbsp;Emily L. Priest,&nbsp;Olivia K. A. Paulin,&nbsp;Léa Lortal,&nbsp;Andrew Donkin,&nbsp;Olivia W. Hepworth,&nbsp;Don N. Wickramasinghe,&nbsp;Aize Pellon,&nbsp;Paul A. Stevens,&nbsp;Leanne Farnan,&nbsp;Adrian Lau,&nbsp;Harun Papini,&nbsp;Pawan Dhami,&nbsp;Sarah L. Gaffen,&nbsp;Jonathan P. Richardson,&nbsp;Julian R. Naglik","doi":"10.1038/s41564-026-02431-2","DOIUrl":"10.1038/s41564-026-02431-2","url":null,"abstract":"Candida albicans is a major opportunistic pathogen in humans that is capable of breaching mucosal barriers and causing severe systemic infections with high mortality. How the host controls mucosal infection and prevents dissemination remains unclear but is essential for improving disease outcomes. Here we demonstrate that C. albicans induces specific IL-1 family members, which are critical for initiating mucosal protection by controlling antimicrobial peptides, IL-17 and neutrophil responses. The loss of combined IL-1 family signalling led to severe oropharyngeal C. albicans infection, which was eventually resolved by a potent neutrophil response. However, in neutropenic conditions, a key patient risk factor, abolishing IL-1 family signalling resulted in C. albicans dissemination, predominantly to the liver, mirroring clinical disease and leading to mortality. This study highlights the IL-1 family as a key initiator of mucosal immunity, restricting mucosal invasion and cooperating with neutrophils to prevent life-threatening systemic infections. IL-1 family signalling drives host mucosal defence against Candida albicans and, together with neutrophils, prevents mucosal–systemic dissemination and life-threatening fungal disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2562-2576"},"PeriodicalIF":18.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02431-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679350","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":"Salmonella uses sulfate reductases with unique catalytic activity to promote gut colonization in mice","authors":"Ju-Sim Kim,&nbsp;Siva Uppalapati,&nbsp;Alyssa Margolis,&nbsp;Michael McClelland,&nbsp;Hanan Elajaili,&nbsp;Eva Nozik,&nbsp;Lin Liu,&nbsp;Andres Vazquez-Torres","doi":"10.1038/s41564-026-02443-y","DOIUrl":"10.1038/s41564-026-02443-y","url":null,"abstract":"Non-typhoidal Salmonella use molybdenum cofactor-containing MopB- or DMSO reductase-family members to respire chemically diverse substrates, including formate, nitrate and methionine sulfoxide, during infection. The DmsABC enzymatic complex encodes one such DMSO reductase to promote oxidative stress resistance. The Salmonella genome encodes several gene paralogues but their role in virulence is unclear. Here we characterize three Salmonella MopB-family extracytoplasmic sulfate reductases, which we call Xsr1A, Xsr2A and Xsr3A. Infection experiments in mice and macrophages show that these sulfate reductases support Salmonella growth and virulence in the gut and during systemic infection, countering the oxidative effects of host respiratory burst activity. Further experiments show that they are molybdenum cofactor-independent enzymes, and instead depend on the nearby redox-active [4Fe–4S] prosthetic group for catalytic activity. Orthologues of these sulfate reductases were found across distant evolutionary branches, suggesting that [4Fe–4S]-dependent catalysis may occur across the ubiquitous MopB superfamily. Our findings offer insights into the modular evolution of redox centres in the widespread MopB superfamily. Extracytoplasmic MopB-family sulfate reductases using Fe–S clusters instead of molybdenum as a cofactor enable sulfate assimilation in Salmonella to support gut colonization and virulence, and help to counter host-imposed oxidative stress.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2619-2633"},"PeriodicalIF":18.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02443-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679339","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":"A microbial PPARadigm for gut protection","authors":"Jonathan Chuck,&nbsp;James V. Parsons,&nbsp;Laura A. Solt","doi":"10.1038/s41564-026-02423-2","DOIUrl":"10.1038/s41564-026-02423-2","url":null,"abstract":"Two independent studies converge on the nuclear receptor PPARα as a key node in gut microbiome communication, highlighting it as a potential therapeutic target in intestinal diseases.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2084-2085"},"PeriodicalIF":18.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612815","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":"Combined phage therapy and faecal microbiota transplantation to treat recurrent urinary tract infection: a case series","authors":"Shawna McCallin,&nbsp;Annika Y. Classen,&nbsp;Simone C. Lieberknecht-Jouy,&nbsp;Fatih Abdula,&nbsp;Sarah Dugas,&nbsp;Oliver Gross,&nbsp;Hendrik Koliwer-Brandl,&nbsp;Swenja Lassen,&nbsp;Jens Scheidegger,&nbsp;Matthew Dunne,&nbsp;Andre Kahles,&nbsp;Jonas Eigler,&nbsp;Fedja Farowski,&nbsp;Paul G. Higgins,&nbsp;Sonja Milek,&nbsp;Oksana Chemych,&nbsp;Jiemin Du,&nbsp;Martin J. Loessner,&nbsp;Thomas M. Kessler,&nbsp;Maria J. G. T. Vehreschild,&nbsp;Lorenz Leitner,&nbsp;Lena M. Biehl","doi":"10.1038/s41564-026-02409-0","DOIUrl":"10.1038/s41564-026-02409-0","url":null,"abstract":"Recurrent urinary tract infections are recalcitrant and difficult-to-treat bacterial infections that primarily affect women. Here we combine phage therapy with faecal microbiota transplantation to decolonize the urinary and intestinal reservoirs of patients with recurrent urinary tract infections. Three women received oral and intravesical phage therapy for 8 days, and two underwent subsequent faecal microbiota transplantation. Treatments were well tolerated, and although Escherichia coli was detected in follow-up samples, patients experienced none or fewer and less severe episodes of urinary tract infection 24 months post-treatment. In a small case series, combined phage therapy and faecal microbiota transplantation was safe and led to sustained reductions in recurrence, severity and antibiotic use in women with recurrent urinary tract infections, even without complete eradication of Escherichia coli.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2112-2118"},"PeriodicalIF":18.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02409-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612602","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":"Focusing on full submissions","authors":"","doi":"10.1038/s41564-026-02452-x","DOIUrl":"10.1038/s41564-026-02452-x","url":null,"abstract":"Nature Microbiology no longer considers presubmission enquiries and instead evaluates all research through full manuscript submissions. This change is intended to improve fairness, rigour and efficiency, ensuring that editorial decisions are based on a complete assessment of the data.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2077-2077"},"PeriodicalIF":18.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02452-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612812","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}