Nature Microbiology最新文献

{"title":"Klebsiella pneumoniae inhibits vasodilation through capsule and T6SS-dependent pathways","authors":"Safi Rehman, Joana Sa-Pessoa, Charlotte Buckley, Rachel L. Lee, Karolina Wojtania, Alix Lee, Rebecca Lancaster, Josy Augustine, Peter Barabas, Ciara Ross, Xun Zhang, John G. McCarron, Tim M. Curtis, Jose A. Bengoechea","doi":"10.1038/s41564-026-02425-0","DOIUrl":"10.1038/s41564-026-02425-0","url":null,"abstract":"Vasodilation is a defence mechanism during inflammation and infection that is regulated by nitric oxide produced by endothelial nitric oxide synthase (eNOS) and the generation of endothelium-dependent hyperpolarization. Several viral infections have been shown to alter vascular biology, but effects of bacterial pathogens are unclear. Here using an ex vivo blood vessel model and human primary endothelial cells, we show that Klebsiella pneumoniae, a prevalent bloodstream pathogen, inhibits vasodilation pathways. The type VI secretion system (T6SS) effector VgrG4 activates the mitochondrial receptor NLRX1, which leads to increased mitochondrial reactive oxygen species and phosphorylation of the eNOS inhibitory site by the kinase PKCβ, which in turn reduces eNOS activity. K. pneumoniae capsule polysaccharide also activates the phosphatase PP2Ac, which reduces phosphorylation of the eNOS activation site. VgrG4-induced mitochondrial reactive oxygen species attenuate endothelium-dependent hyperpolarization by impairing signalling of the Ca2+-activated K+ channel axis. This work reveals that T6SS activity can modulate host vascular biology by targeting eNOS post-translational modifications. Vasodilation is inhibited by Klebsiella pneumonia through a multipronged approach involving type VI secretion system activity and the VgrG4 effector, plus capsule, to limit eNOS-dependent and endothelial hyperpolarization routes to vasodilation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2170-2186"},"PeriodicalIF":18.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02425-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550066","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":"Molecular and cellular insights into the parasitic infection of bloom-forming marine diatoms by Pirsonia diadema","authors":"Varsha Mathur, Nicholas A. T. Irwin, Luis Javier Galindo, Elisabet Alacid, Kevin Moog, Elliot Flaum, Gautam Dey, Flora Vincent, Michael Cunliffe, Sunju Kim, Ulrich Technau, Thomas A. Richards","doi":"10.1038/s41564-026-02421-4","DOIUrl":"10.1038/s41564-026-02421-4","url":null,"abstract":"Microbial host–parasite interactions shape global biogeochemical cycles, yet their cellular and evolutionary mechanisms remain poorly understood. Here we developed a model pathosystem to explore the interaction between the eukaryotic microparasite, Pirsonia diadema, and its host, the bloom-forming diatom, Coscinodiscus. Culture conditions recapitulated Pirsonia’s rapid life cycle in vitro, and live-cell imaging enabled the quantitative analysis of infection dynamics and host mortality. Genome sequencing and time-resolved dual RNA sequencing of Pirsonia revealed unique genetic innovations relative to their oomycete relatives and an upregulation of an expanded multi-gene family of integrin-like proteins in Pirsonia zoospores during infection. Targeted drug perturbations combined with ultrastructure expansion microscopy confirm stage specific roles for Pirsonia’s cytoskeleton, including actin-dependent host attachment and formation of intracellular parasite-induced feeding structures and microtubule-associated processes in zoospore differentiation. Together, these findings reveal mechanisms underpinning Pirsonia infection and provide insights into the evolution of strategies that underpin parasitic shunts in marine trophic networks. Ultrastructure expansion microscopy, live-cell imaging and time-resolved dual RNA sequencing reveal the infection dynamics of a microparasite, providing insights into how Pirsonia diadema shapes marine trophic networks.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2478-2492"},"PeriodicalIF":18.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02421-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550131","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":"Mapping in-cell protein contact sites reveals hijacking of paraspeckles during influenza A virus infection","authors":"Iuliia Kotova, Lars Mühlberg, Konstantin Gilep, Mira Lea Burtscher, Isabelle Becher, Dingquan Yu, Daniel Ziemianowicz, Stephanie Stanelle-Bertram, Sebastian Beck, Kyungmin Baeg, Alexandra Grba, Olivier Duss, Gülşah Gabriel, Mikhail M. Savitski, Fan Liu, Boris Bogdanow, Jan Kosinski","doi":"10.1038/s41564-026-02416-1","DOIUrl":"10.1038/s41564-026-02416-1","url":null,"abstract":"Influenza A virus (IAV) hijacks host cellular machinery during infection but many host–virus protein interactions remain uncharacterized, particularly in their native context. Here, we applied in-cell cross-linking mass spectrometry, integrated with structural modelling and functional assays, to map protein–protein contact sites in IAV-infected human cells. This revealed previously unrecognized virus–host interactions linked to spatially organized processes. We identified host factors linked to the maturation of distinct glycoforms of the viral surface glycoprotein haemagglutinin through the membrane-bound endoplasmic reticulum–Golgi system. In the nucleus, we observed the progressive disassembly of paraspeckles (phase-separated membraneless compartments) across multiple cell lines. Mechanistically, viral nucleoprotein and non-structural protein 1 interact with host paraspeckle proteins, the viral endonuclease PA-X degrades long non-coding RNA housed within paraspeckles and viral RNA polymerase II is inhibited to drive paraspeckle disruption, which releases host factors that facilitate IAV replication. These findings uncover mechanisms by which IAV exploits and remodels host compartments during infection. In-cell cross-linking mass spectrometry maps protein contacts in influenza-infected human cells, revealing how the virus hijacks host membrane-trafficking factors and dismantles nuclear paraspeckles to enhance replication.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2247-2265"},"PeriodicalIF":18.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02416-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522073","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":"All-trans retinoic acid suppresses systemic inflammation induced by severe fever with thrombocytopenia syndrome virus in mice","authors":"Xin Yu, Jianan Wu, Xiaohong Yin, Mengjia Yue, Yunfa Zhang, Jinxin Meng, Jinyan Xie, Jialei Li, Xiaoai Zhang, Ning Cui, Zhen Wang, Zhi-You Wang, Wen-Wen Zhang, Xinyu Ni, Shuxian Chen, Hao Li, Wei Liu, Shu Jeffrey Zhu","doi":"10.1038/s41564-026-02411-6","DOIUrl":"10.1038/s41564-026-02411-6","url":null,"abstract":"The vitamin A metabolite all-trans retinoic acid (ATRA) has immunoregulatory features, but its systemic role during viral infection is unclear. Here we show that patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne infection, have depleted serum vitamin A and ATRA levels. This correlated with exacerbated systemic inflammatory response syndrome severity and mortality risk. In an SFTSV mouse model, intraperitoneal administration of ATRA suppresses virus-induced hyperinflammation via peroxisome proliferator-activated receptor-γ (PPARγ), which downregulates the transcriptional activity of activator protein-1 (AP-1 in macrophages. Mechanistically, ATRA binds retinoid X receptor-α (RXRα) and facilitates the formation of RXRα–PPARγ heterodimers. This complex sequesters the transcription factor JUN and suppresses the expression of AP-1 promoter-dependent genes, such as IL-6, thus attenuating inflammatory signalling pathways. Our study suggests a retinoid-mediated immunometabolic checkpoint during SFTSV infection and proposes retinoid signalling as a therapeutic target for cytokine storm management. Depletion of the vitamin A metabolite all-trans retinoic acid (ATRA) in patients infected with severe fever with thrombocytopenia syndrome virus correlates with severe inflammation. In mice, ATRA supplementation reduces IL-6 levels and hyperinflammation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2279-2293"},"PeriodicalIF":18.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02411-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522075","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":"Predictable shifts in microbial species composition lead to community-wide robustness to environmental stress","authors":"Jana S. Huisman, Martina Dal Bello, Jeff Gore","doi":"10.1038/s41564-026-02422-3","DOIUrl":"10.1038/s41564-026-02422-3","url":null,"abstract":"Environmental stress reduces species growth rates, but how it impacts microbial community function is less clear. Here we experimentally demonstrate that increasing salinity stress shifts community composition towards species with higher growth rates. This shift leads the mean community growth rate to be more robust to increasing stress than the growth of individual species. We demonstrate this by propagating natural aquatic communities at multiple salinities and mapping the observed diversity onto the measured salinity performance curves of more than 80 bacterial isolates. We validated these results with pairwise in vitro species competitions and using 16S data of microbial communities from estuarine environments. A generalized Lotka–Volterra model including mortality and salinity-dependent growth rates recapitulates the observed robustness of community growth sustained by more abundant faster growers at high salinity. These results could be extended to other environmental stressors, pointing to a fundamental mechanism with which communities maintain growth despite deteriorating conditions. Environmental stress shifts microbial composition towards species with high growth rates, providing community-wide protection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2310-2320"},"PeriodicalIF":18.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02422-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459584","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":"Bacillus subtilis cells can escape biofilms by producing a hydrogel that ejects them","authors":"","doi":"10.1038/s41564-026-02430-3","DOIUrl":"10.1038/s41564-026-02430-3","url":null,"abstract":"Bacillus subtilis biofilms can disperse by ejecting motile cells using osmotic pressure generated by a secreted hydrogel. This mechanism of biofilm dispersal has mechanistic parallels to a process in evolutionarily distant Cnidaria and might inform new therapeutic approaches to control biofilm dispersion.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2395-2396"},"PeriodicalIF":18.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459587","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":"New nucleases target modified DNA","authors":"Jason J. Gill","doi":"10.1038/s41564-026-02418-z","DOIUrl":"10.1038/s41564-026-02418-z","url":null,"abstract":"Bacteriophages often use hypermodified DNA to protect themselves from host defences. The END nucleases found in bacteria represent a new class of modification-dependent endonucleases recognizing diverse DNA modifications, allowing a single system to protect the cell against multiple phage types.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2082-2083"},"PeriodicalIF":18.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432118","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":"Self-generated hydrogel ejects bacterial cells for localized biofilm dispersion","authors":"Todd Kwang-Tao Chou, Alejandra Dau-Martinez, Júlia Vicens-Figueres, Arvind Gouttumukkala, Leticia Galera-Laporta, Jordi Garcia-Ojalvo, Gürol M. Süel","doi":"10.1038/s41564-026-02413-4","DOIUrl":"10.1038/s41564-026-02413-4","url":null,"abstract":"Bacteria residing in biofilms are embedded in an extracellular matrix. Whereas biofilm formation is well studied, less is known about biofilm dispersion, although enzymatic extracellular matrix degradation is suspected to play a key role. Here we show that Bacillus subtilis biofilms can alternatively eject a specific cell type, locally and anisotropically, using mechanical forces arising from a self-generated hydrogel. Single-cell resolution imaging combined with mathematical modelling, and chemical and genetic perturbations, show that the production of the extracellular poly-γ-glutamic acid (γ-PGA) polymer is necessary to drive this cell ejection. Specifically, osmotic pressure from the γ-PGA hydrogel propels interior cells through the outer layers to break free from the biofilm. We demonstrate control over this process through γ-PGA modulation such that biofilm dispersion can be either inhibited or promoted. Forceful ejection driven by γ-PGA has so far only been described in marine organisms such as jellyfish. Our discovery of biofilm cell ejection via γ-PGA thus reveals not only a previously uncharacterized biofilm dispersion mechanism but also an unexpected mechanistic parallel to evolutionarily distant Cnidaria. Bacillus subtilis biofilms locally disperse by ejecting motile cells through osmotic pressure generated by their poly-γ-glutamic acid hydrogel, a mechanism resembling that through which Cnidaria eject nematocysts.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2423-2435"},"PeriodicalIF":18.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02413-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400666","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":"Non-canonical gene amplifications facilitate adaptive evolution in bacteria","authors":"Idan Yelin, Roy Kishony","doi":"10.1038/s41564-026-02415-2","DOIUrl":"10.1038/s41564-026-02415-2","url":null,"abstract":"Gene amplification, a common route to bacterial adaptation, often occurs through recombination between two copies of an insertion sequence (IS) element flanking a genomic region. Alternative non-canonical structures have also been proposed, in which a duplication is formed by a single IS element whose two ends join two distant chromosomal loci. However, the prevalence of such non-canonical structures and their role in bacterial adaptive evolution remain unclear. Here we developed AmpliFinder, a computational tool that uses short-read sequencing data to systematically identify pairs of IS–chromosome junctions that correspond to the two ends of the same IS element yet map to distant genomic loci flanking amplified regions. Applying AmpliFinder to 10,347 laboratory-evolved Escherichia coli and Acinetobacter baumannii isolates, we identified 113 distinct de novo IS-associated amplifications and found that non-canonical amplifications are the most abundant mode of amplification. We validated the inferred architectures using ultra-long-read sequencing and propose a model for non-canonical amplification formation supported by the observation of nested intermediate structures. Quantifying enrichment for antibiotic-resistance genes in amplicons, we find that non-canonical amplifications more effectively and narrowly amplify genes under selection. These results highlight the role of non-canonical IS-based amplifications in the adaptive evolution of bacteria. Transposon-associated amplifications are dominated by a previously underappreciated architecture, where the transposon is found only between, not flanking, the amplicons. These amplifications facilitate the evolution of bacteria and their adaptation to antibiotics.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2201-2212"},"PeriodicalIF":18.7,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02415-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393403","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":"Identification of genetic markers of quinine partial resistance in Plasmodium falciparum","authors":"Mariko Kanai, Sachel Mok, Tomas Yeo, Melanie J. Shears, Jin H. Jeon, Sunil K. Narwal, Leila S. Ross, Kharizta Wiradiputri, Meseret T. Haile, Abhai K. Tripathi, Godfree Mlambo, Jonathan Kim, Eva Gil-Iturbe, Heekuk Park, Tolla Ndiaye, John Okombo, Kurt E. Ward, Felix D. Rozenberg, Kate J. Fairhurst, Sydney M. Gavula, Talia S. Bloxham, Jessica L. Bridgford, Tanaya Sheth, Manuel Llinás, Marcus C. S. Lee, Jennifer L. Small-Saunders, Filippo Mancia, Matthias Quick, Anne-Catrin Uhlemann, Photini Sinnis, David Armand Fidock","doi":"10.1038/s41564-026-02410-7","DOIUrl":"10.1038/s41564-026-02410-7","url":null,"abstract":"The genetic basis of Plasmodium falciparum resistance to quinine, a drug used to treat severe malaria, has long been unclear. To investigate this, here we used a human liver-chimaeric mouse model to conduct a P. falciparum genetic cross between quinine-partially resistant and quinine-sensitive parasites. Drug profiling and quantitative trait loci analyses of 120 unique recombinant progeny mapped resistance to segments on chromosomes 7 and 12, indicating a polygenic basis. The chloroquine resistance transporter PfCRT and a structurally similar putative drug/metabolite transporter, DMT1, were identified as primary chromosome 7 candidates based on gene-editing studies. In a proteoliposome assay, both mutant DMT1 and PfCRT transported more quinine than their wild-type isoforms. DMT1 localized to the P. falciparum digestive vacuole, lipid bodies, parasitophorous vacuolar membrane and structures associated with vesicular trafficking. An ATP-dependent zinc metalloprotease (FtsH1) on chromosome 12 also modulated quinine and chloroquine resistance. We suggest that genotypic surveillance of these markers should be performed in clinical settings of quinine use. A genetic cross of Plasmodium falciparum parasites revealed that quinine resistance is polygenic and is associated with mutations in transporter proteins on chromosome 7 (PfCRT and DMT1) and a metalloprotease on chromosome 12 (FtsH1), highlighting key markers for clinical surveillance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 8","pages":"2213-2231"},"PeriodicalIF":18.7,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02410-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393777","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}