Nature Microbiology最新文献

{"title":"Gasdermins against intracellular bacterial pathogens","authors":"Fernando W. Souza, Yaxin Liu, Jacqueline Trujillo, Edward A. Miao","doi":"10.1038/s41564-026-02272-z","DOIUrl":"10.1038/s41564-026-02272-z","url":null,"abstract":"Intracellular bacterial pathogens can cause high levels of morbidity and mortality in humans. Host immune responses that protect against these infections include pyroptosis, a form of lytic cell death caused by the insertion of large gasdermin (GSDM) pores into the host plasma membrane. Here we review recent advances in our understanding of how the five GSDM proteins, GSDMA–E, are activated by distinct signalling pathways. Pyroptosis can both eliminate intracellular niches and release cytosolic interleukin-1 family cytokines that further prime host immune responses against the invading pathogen. Because pyroptosis targets microbes, host-adapted intracellular pathogens have evolved strategies to efficiently subvert it. However, environmental pathogens fail to evade, making pyroptosis a potent barrier against infection. We summarize recent findings for the host-adapted bacterial pathogens Shigella flexneri, Salmonella enterica serovar Typhimurium and Mycobacterium tuberculosis, contrasted with the environmental bacteria Burkholderia thailandensis and Chromobacterium violaceum. This Review discusses recent advances in our understanding of how gasdermins are activated by distinct signalling pathways and summarizes recent findings from host-adapted bacterial pathogens contrasted with environmental bacteria.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"624-637"},"PeriodicalIF":19.4,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223281","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 microbial ammonia enhances colonic acetylcholine levels to regulate intestinal motility","authors":"Hao Chen, Zhen Wang, Yiming Zhao, Wenyu Yang, Jing Huang, Zheng Yu","doi":"10.1038/s41564-026-02269-8","DOIUrl":"10.1038/s41564-026-02269-8","url":null,"abstract":"Intestinal motility is a function of the enteric nervous system involving secretion of the excitatory neurotransmitter acetylcholine (ACh). Although gut commensal bacteria are key regulators of intestinal physiology, the molecular mechanisms underlying microbial influence on intestinal peristalsis and constipation remain unclear. Here we report a link between microbial nitrogen metabolism and intestinal motility regulation via ammonia production. We observed compensatory elevation of intestinal ammonia levels and urease activity in mouse models of intestinal dysmotility, induced by ACh deficiency, and in patients with constipation. Ammonia supplementation or intervention in mice with the urease-positive Lysinibacillus fusiformis isolated from patient stool, or engineered urease-expressing bacteria, effectively restored colonic ACh levels. In vitro, ammonia upregulated the expression of voltage-gated calcium channels on enteric neurons, driving Ca2+ influx to potentiate ACh secretion. Our study reveals a microbial compensatory mechanism that responds to fluctuating ACh levels in the intestine and provides microbial targets for intestinal motility disorders. Intestinal motility defects caused by lower acetylcholine levels in the gut are compensated by bacteria that generate ammonia from urea which facilitates the release of acetylcholine via upregulation of voltage-gated channels on enteric neurons.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"907-919"},"PeriodicalIF":19.4,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223282","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":"How taurine keeps asymptomatic malaria infections in check","authors":"Terrie E. Taylor","doi":"10.1038/s41564-026-02276-9","DOIUrl":"10.1038/s41564-026-02276-9","url":null,"abstract":"Seasonal variations in plasma taurine concentrations may allow Plasmodium falciparum infections to avoid splenic clearance during the dry season.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"617-618"},"PeriodicalIF":19.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223318","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":"Conserved CD4+ T cell staphylococcal and streptococcal epitopes enable broad-acting vaccines in mice","authors":"Jessica Braverman, Ian R. Monk, Adrianna M. Turner, Asolina Braun, Heran Zhang, Shanzou Chung, Claerwen M. Jones, Pirooz Zareie, Nicole L. La Gruta, Joanne Rimmer, Glen P. Carter, Benjamin P. Howden, Nancy Wang, Anthony W. Purcell, Timothy P. Stinear, Linda M. Wakim","doi":"10.1038/s41564-026-02265-y","DOIUrl":"10.1038/s41564-026-02265-y","url":null,"abstract":"Vaccines are effective and much-needed tools against bacterial infection, which mitigate multidrug resistance; however, selection of bacterial antigens that elicit protection and contribute to effective vaccines remains challenging. Here we use immunopeptidomics to identify CD4+ T cell vaccine targets in methicillin-resistant Staphylococcus aureus, a clinically significant, antibiotic-resistant bacterium that is susceptible to T cell-mediated control. We identified a highly conserved, immunodominant CD4+ T cell epitope in S. aureus that is derived from the core DNA-binding protein Hu (Hup). This epitope was shared across a range of clinically relevant streptococcal and staphylococcal species, and cross-species-reactive Hup-specific CD4+ T cells were found in both mice and humans. Immunization of mice with the Hup epitope resulted in the development of broadly protective CD4+ T cell immunity capable of limiting disease severity following infection with S. aureus and Streptococcus pneumoniae. These findings suggest that vaccines incorporating antigens derived from core genes conserved across species might confer broad-spectrum protection against multiple clinically relevant, antibiotic-resistant streptococcal and staphylococcal strains. Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"731-746"},"PeriodicalIF":19.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223319","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":"Longitudinal plasma metabolomics reveals a role for taurine in asymptomatic malaria and seasonal persistence","authors":"Gretchen Diffendall, Perine Millot, Patty Chen, Balotin Fogang, Dominique Dorin-Semblat, Fanny Aprahamian, Sylvère Durand, Benoît Gamain, Antoine Claessens, Artur Scherf","doi":"10.1038/s41564-026-02268-9","DOIUrl":"10.1038/s41564-026-02268-9","url":null,"abstract":"In malaria-endemic regions, asymptomatic Plasmodium falciparum infections during periods of low transmission alternate with symptomatic infections during periods of high transmission. The mechanisms underlying P. falciparum persistence without causing symptoms during low-transmission periods remain unclear. Here we analysed the plasma metabolome (n = 199) of individuals in the Gambia, West Africa, during the high and low malaria transmission periods. We observed significant metabolome changes associated with seasonality and to a lesser extent with malaria pathogenicity. We show that plasma levels of taurine, an amino sulfonic acid, increase longitudinally during periods of low transmission. Although taurine showed no effect on the development of cultured parasites in vitro, it strongly inhibited and prevented malaria-infected red blood cell (iRBC) adhesion via PfEMP1 to the common adhesion receptor CD36 and the endothelial protein C receptor, which is linked to cerebral malaria. We reveal a role for taurine in reducing cytoadhesion, which could inform strategies to reduce symptomatic malaria in sub-Saharan Africa. Seasonal metabolomics revealed that taurine increases during low malaria transmission and is linked to asymptomatic Plasmodium falciparum infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"678-689"},"PeriodicalIF":19.4,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210123","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":"Candida auris vacuolar calcium pump mediates fluconazole efflux and resistance evolution","authors":"Yabing Song, Jinxin Chen, Junhua Wan, Jiamo Zhang, Qizheng Liu, Fei Sun, Hanlin Zhang, Yuru Guo, Eve W. L. Chow, Yali Chen, Ziyu Yan, Jianbin Wang, Kun Chen, Yue Wang, Jiaxin Gao","doi":"10.1038/s41564-026-02270-1","DOIUrl":"10.1038/s41564-026-02270-1","url":null,"abstract":"Candida auris is an emerging fungal pathogen notable for its intrinsically high resistance to fluconazole, the most prescribed antifungal drug. However, the genetic regulators underlying fluconazole susceptibility in C. auris remain unclear. Here we performed a pooled screen of piggyBac (PB) transposition mutants and identified significant enrichment of mitochondrial genes whose inactivation reduces fluconazole susceptibility. A genome-wide genetic interaction analysis of a mitochondrial gene deletion mutant, pet309Δ, suggests that the vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) is responsible for its reduced fluconazole susceptibility. Fluconazole induces significant upregulation of CDT1 through the calcineurin signalling pathway. Cdt1, beyond its canonical calcium-pumping function, has evolved another function in mediating fluconazole efflux through its fluconazole-induced, calcineurin- and ATP hydrolysis-dependent plasma membrane localization. In addition, Cdt1 accelerates the evolution of fluconazole resistance or tolerance, and its transcript levels are substantially elevated across resistant clinical isolates. Our findings reveal a neofunctionalized role for Cdt1 in mediating fluconazole efflux in C. auris. The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"786-801"},"PeriodicalIF":19.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204971","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":"Human immunodeficiency virus-associated gut microbiome impacts systemic immunodeficiency and susceptibility to opportunistic gut infection","authors":"Stavros Bashiardes, Melina Heinemann, Lorenz Adlung, Rafael Valdés-Mas, Jemal Ali Mahdi, Samuel P. Nobs, Timur Tuganbaev, Takahiro Yamada, Max Horn, Uria Mor, Yotam Cohen, Sarah Israel, Maya Korem, Yonatan Oster, Karen Olshtain-Pops, Efrat Orenbuch-Harroch, Muhammed Dervis Arslan, Shahar Molina, Maya Zur, Shimrit Eliyahu-Miller, Aurélie Bukimer, Sara Federici, Mally Dori-Bachash, Nira Amar, Daniel Elbirt, Ronit Cohen-Poradosu, Dan Turner, Tiberiu Hershcovici, Elez Vainer, Noa Stettner, Alon Harmelin, Hailay Gebremeskel, Yazezew Kebede, Sabine Schmidt, Niv Zmora, Arunraj Dhamodaran, Jens Puschhof, Zvi Bentwich, Hagit Shapiro, Ido Amit, Hila Elinav, Eran Elinav","doi":"10.1038/s41564-025-02253-8","DOIUrl":"10.1038/s41564-025-02253-8","url":null,"abstract":"The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from Bacteroides to Prevotella species in an Israeli cohort and multiple Enterobacteriaceae species including Escherichia coli and Klebsiella quasivariicola in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4+ T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4+ T cell counts induced colonic epithelium-associated CD4+ T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from Cryptosporidium parvum infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity. Human immunodeficiency virus (HIV)-associated gut microbiome dysbiosis correlates with systemic immunodeficiency and opportunistic gut infections. Faecal microbiome transplantation from people living with HIV with high peripheral CD4+ T cell counts improved intestinal immunity and protection against Cryptosporidium parvum in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"690-703"},"PeriodicalIF":19.4,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204973","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":"Realizing phage therapy in the UK","authors":"Michael A. Brockhurst, Joanne L. Fothergill, Stineke van Houte, Edze R. Westra","doi":"10.1038/s41564-026-02280-z","DOIUrl":"10.1038/s41564-026-02280-z","url":null,"abstract":"On 25 November 2025, the international phage therapy research and biotechnology communities gathered in Liverpool, UK, to discuss progress in implementing clinical phage therapies and the latest technological breakthroughs in phage biology and engineering, while UK regulators and health agencies provided the latest guidance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"619-621"},"PeriodicalIF":19.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195068","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":"Targeted innate immune inhibition therapy compared with antibiotics for recurrent acute cystitis: a randomized, open-label phase 2 trial","authors":"Ines Ambite, Adrian Pilatz, Mareike Buch-Heberling, Shahram Ahmadi, Gabriela Godaly, Florian Wagenlehner, Catharina Svanborg","doi":"10.1038/s41564-026-02262-1","DOIUrl":"10.1038/s41564-026-02262-1","url":null,"abstract":"Cystitis is a bacterial infection of the bladder that occurs in about half of women at least once in their lifetime. Antibiotics such as nitrofurantoin are used to treat cystitis, but antibiotic resistance is a concern, especially for recurrent infections. Here we report an open-label, randomized, single-centre, phase 2 study to analyse the acute and long-term safety and efficacy of the IL-1 receptor antagonist anakinra, compared with nitrofurantoin, in recurrent cystitis. A total of 30 adult female patients with a documented history of recurrent cystitis and a current acute cystitis episode were randomized in a 2:1 ratio to treatment with anakinra (n = 20) or nitrofurantoin (n = 10) for 5 days. Primary and secondary efficacy end-points were reached, defined as the reduction in typical symptoms, measured by the acute cystitis symptom score (day 5), longitudinal symptom scores, recurrence rates, quality of life, gene expression analysis and microbiology at follow-up on days 15 and 30 and at 6 months. Symptom scores were decreased in the anakinra (P < 0.001) and nitrofurantoin (P < 0.001) arms after 5 days and remained low after 15 days, 30 days and 6 months. Recurrences were less frequent after 6 months in both treatment groups compared with the 6-month pre-enrolment history (P < 0.001 for anakinra and P = 0.004 for nitrofurantoin), and the quality of life was increased, without adverse effects. Immune gene expression was rapidly inhibited in the anakinra-treated patients but not in the nitrofurantoin group. Targeted innate immune inhibition therapy shows non-inferiority to nitrofurantoin in patients with recurrent acute cystitis. German Clinical Trials Register ID: DRKS00025964 . An open-label, randomized, single-centre, phase 2 study shows that the IL-1 receptor antagonist anakinra shows non-inferiority to the antibiotic nitrofurantoin in patients with recurrent acute cystitis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"638-647"},"PeriodicalIF":19.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02262-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181203","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":"Addendum: ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro","authors":"Lejla Daruka, Petra Szili, Márton Simon Czikkely, Zoltán Farkas, Csaba Pál","doi":"10.1038/s41564-026-02267-w","DOIUrl":"10.1038/s41564-026-02267-w","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"833-835"},"PeriodicalIF":19.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02267-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132301","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}