Nature Microbiology最新文献

{"title":"Author Correction: Characterization of an amyloid-based antiphage defence system in Escherichia coli.","authors":"Léa Ibarlosa, Sonia Dheur, Corinne Sanchez, Seamoon Deb, Alexandra Granger-Farbos, Virginie Coustou, Mélanie Berbon, Aurélie Massoni-Laporte, Bénédicte Salin, Corinne Blancard, Claire Saragaglia, Xavière Menatong Tene, Nicolas Dufour, Ombeline Rossier, Birgit Habenstein, Laurent Debarbieux, Brice Kauffmann, Antoine Loquet, Sven J Saupe","doi":"10.1038/s41564-025-02181-7","DOIUrl":"https://doi.org/10.1038/s41564-025-02181-7","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302054","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":"The IFIT2-IFIT3 antiviral complex targets short 5' untranslated regions on viral mRNAs for translation inhibition.","authors":"Dustin R Glasner,Candace Todd,Brian Cook,Agustina D'Urso,Shivani Khosla,Elena Estrada,Jaxon D Wagner,Mason D Bartels,Chuan-Tien Hung,Pierce Ford,Jordan Prych,Kathryn S Hatch,Brian A Yee,Kaori M Ego,Qishan Liang,Sarah R Holland,James Brett Case,Kevin D Corbett,Michael S Diamond,Benhur Lee,Gene W Yeo,Mark A Herzik,Eric L Van Nostrand,Matthew D Daugherty","doi":"10.1038/s41564-025-02138-w","DOIUrl":"https://doi.org/10.1038/s41564-025-02138-w","url":null,"abstract":"Recognition of foreign RNA is critical for the innate immune response to viruses. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFIT) 2 and 3 are highly upregulated following viral infection, but mechanistic insight into their antiviral role is lacking. Here we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can serve as a molecular pattern for innate immune recognition via IFIT2 and IFIT3. Structure determination of the IFIT2-IFIT3 complex at 3.2 Å using cryo-EM reveals a domain-swapped heterodimer that is required for recognition of the viral mRNA 5' end, translation inhibition and antiviral activity. Critically, viral or host 5' UTR lengths less than 50 nucleotides are necessary and sufficient to enable translation inhibition by the IFIT2-IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5' UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2-IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"1 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296123","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":"Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses.","authors":"Alexandra A Abu-Shmais,Gray Freeman,Adrian Creanga,Matthew J Vukovich,Tek Malla,Grace E Mantus,Geoffrey D Shimberg,Rebecca A Gillespie,Vanessa Guerra Canedo,Bernadeta Dadonaite,Megan D Rodgers,Ankita J Chopde,Elizabeth Bardwil-Lugones,Tatsiana Bylund,Amy R Henry,Jesmine Roberts-Torres,Timothy S Johnston,Sarah Smith,Eun Sung Yang,Cheng Cheng,Emma L Walker,Michelle Ravichandran,Ingelise J Gordon,Tejaswi S Dittakavi,Douglas S Reed,Theodore C Pierson,Lesia Dropulic,Jesse D Bloom,Yaroslav Tsybovsky,Eli A Boritz,Daniel C Douek,Tongqing Zhou,Masaru Kanekiyo,Sarah F Andrews","doi":"10.1038/s41564-025-02137-x","DOIUrl":"https://doi.org/10.1038/s41564-025-02137-x","url":null,"abstract":"Highly pathogenic avian influenza H5Nx viruses are an emerging threat for global health, especially clade 2.3.4.4b H5N1 virus which causes panzootic infections. Here we describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. By screening over 500 mAbs, we identified 5 mAbs that neutralized the majority of H5 clades including 2.3.4.4b and target three distinct conserved epitopes within the HA globular head. Cryo-electron microscopy structures of these mAbs in complex with HA, deep mutational scanning and neutralization escape studies define the sites of vulnerability of H5 HA. These mAbs mediated stronger prophylactic protection against clade 2.3.4.4b H5N1 infection in mice than the best-in-class mAb targeting the HA stem. Our study identified several highly potent broadly neutralizing H5 mAbs from humans that either alone or in combination provide a pragmatic pandemic preparedness option against the threat of panzootic H5N1 influenza.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"37 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288396","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":"Dipeptidase 1 is a functional receptor for a porcine coronavirus.","authors":"Jérémy Dufloo,Ignacio Fernández,Atousa Arbabian,Ahmed Haouz,Nigel Temperton,Luis G Gimenez-Lirola,Félix A Rey,Rafael Sanjuán","doi":"10.1038/s41564-025-02111-7","DOIUrl":"https://doi.org/10.1038/s41564-025-02111-7","url":null,"abstract":"Coronaviruses of the subgenus Embecovirus include several important pathogens, such as the human seasonal coronaviruses HKU1 and OC43, bovine coronavirus and porcine haemagglutinating encephalomyelitis virus (PHEV). While sialic acid is thought to be required for embecovirus entry, protein receptors remain unknown for most of these viruses. Here we show that PHEV does not require sialic acid for entry and instead uses dipeptidase 1 (DPEP1) as a receptor. Cryo-electron microscopy at 3.4-4.4 Å resolution revealed that, unlike other embecoviruses, PHEV displays both open and closed conformations of its spike trimer at steady state. The spike receptor-binding domain (RBD) exhibits extremely high sequence variability across embecoviruses, and we found that DPEP1 usage is specific to PHEV. In contrast, the X-ray structure of the RBD-DPEP1 complex at 2.25 Å showed that the structural elements involved in receptor binding are conserved, highlighting the remarkable versatility of this structural organization in adopting novel receptor specificities.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"37 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261301","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":"Drought stress fosters collaboration between wheat and microbes.","authors":"Oluwaseyi Samuel Olanrewaju,Lucy Moleleki","doi":"10.1038/s41564-025-02156-8","DOIUrl":"https://doi.org/10.1038/s41564-025-02156-8","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"28 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261541","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":"Toxoplasma gondii VIP1 mediates parasitophorous vacuole-host endoplasmic reticulum interactions to facilitate parasite development.","authors":"Julia D Romano,Ruth Buh,Tanner Grudda,Julia R Box,John Beltran,Shahbaz M Khan,Isabelle Coppens","doi":"10.1038/s41564-025-02144-y","DOIUrl":"https://doi.org/10.1038/s41564-025-02144-y","url":null,"abstract":"Membrane contact sites (MCS) are areas of close apposition between organelles without membrane fusion, allowing for exchange of biomolecules. The endoplasmic reticulum (ER) forms many MCS via two proteins, vesicle-associated membrane protein-associated proteins A and B (VAPA and VAPB). The obligate intracellular parasite Toxoplasma gondii resides within mammalian cells in a parasitophorous vacuole (PV), which closely contacts the host ER at distances compatible with MCS. However, the proteins mediating this interaction remain largely unknown. Here, using molecular and microscopy approaches, we show that VAPA and VAPB localize at the PV membrane and, with motile sperm domain-containing protein 2 (MOSPD2), mediate ER-PV interactions. Cells deficient in VAPA, VAPB and MOSPD2 do not recruit host ER at the PV, and parasites show growth defects. We identify a parasite protein that localizes at the PV membrane, called TgVIP1, which harbours an FFAT-like motif that binds VAPA and VAPB. These findings lay the basis for understanding how and why Toxoplasma exploits ER-PV interactions and may uncover new drug targets.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"88 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261283","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":"A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics.","authors":"Kuan-Yi Lu,Xiangbo Yang,Matthew J G Eldridge,Rongfeng Sun,Rachel T Giorgio,Benjamin I Morris,Nikki J Wagner,Brian Hardy,Matthew Axtman,Sarah E Rowe,Xiaodong Wang,Vance G Fowler,Qingyun Liu,Sophie Helaine,Kenneth H Pearce,Brian P Conlon","doi":"10.1038/s41564-025-02124-2","DOIUrl":"https://doi.org/10.1038/s41564-025-02124-2","url":null,"abstract":"Intracellular bacterial reservoirs contribute to antibiotic treatment failure by fostering metabolically dormant persister cells that are highly tolerant to killing. However, strategies to effectively target intracellular persister cells remain limited. Here we developed a high-throughput screen to identify compounds that modulate the metabolic activity of intracellular Staphylococcus aureus. The identified compound, KL1, increases intracellular bacterial metabolic activity and sensitizes persister populations of S. aureus to antibiotics, without causing cytotoxicity or bacterial outgrowth. KL1 also exhibits adjuvant activity against intramacrophage Salmonella enterica Typhimurium and Mycobacterium tuberculosis, as well as in murine infection models of S. aureus and S. Typhimurium infection. Transcriptomic analysis and further mechanistic studies reveal that KL1 modulates host immune response genes and suppresses the production of reactive species in host macrophages, alleviating a key inducer of antibiotic tolerance. Our findings highlight the potential to target intracellular persisters by stimulating their metabolism. There are two major problems in the field of antimicrobial chemotherapy-antibiotic resistance and antibiotic tolerance. Antibiotic tolerance has been frequently connected with poor treatment outcomes in the clinic. Unlike antibiotic resistance, which permits bacterial growth in the presence of drugs, antibiotic tolerance allows bacteria to withstand multiple antibiotics for prolonged periods. The extended survival of tolerant bacteria further predisposes them to evolve antibiotic resistance over time, underscoring the critical need to address antibiotic tolerance. Host interactions have been shown to induce persister formation in numerous pathogens, with the production of reactive oxygen and nitrogen species heavily implicated in the collapse of bacterial metabolic activity and entry into an antibiotic-tolerant state. Yet, tools to study or target this process remain limited. Here we developed a high-throughput screen to identify compounds that modulate intracellular S. aureus metabolism, leading to the discovery of KL1, a host-directed compound that sensitizes persisters to antibiotic killing.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"39 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261533","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":"Mycobacterium tuberculosis-derived linoleic acid increases regulatory T cell function to promote bacterial survival within macrophages.","authors":"Hongyu Cheng,Shenzhi Li,Hongjie Liu,Meiyi Yan,Jingxiang Wang,Jingping Huang,Shanshan Liu,Yifan Yang,Xinyu Cao,Pengfei Cui,Yuanna Cheng,Zhonghua Liu,Jie Wang,Xiaochen Huang,Lin Wang,Lianhua Qin,Ruijuan Zheng,Carl G Feng,Qiang Zou,Yicheng Sun,Zhe Ji,Hua Yang,Baoxue Ge","doi":"10.1038/s41564-025-02140-2","DOIUrl":"https://doi.org/10.1038/s41564-025-02140-2","url":null,"abstract":"Regulatory T (Treg) cells expand during Mycobacterium tuberculosis (Mtb) infection and suppress T cell-mediated control. Whether Mtb actively contributes to this process is unclear. Here, using a genome-wide mutant library, we show that the expression of Mtb Rv1272c, an ATP-binding cassette transporter, increased under hypoxic conditions and promotes Mtb survival in vivo by increasing lecithin import, followed by the production and release of linoleic acid. Linoleic acid released by infected macrophages promoted surface trafficking of the immune checkpoint molecule cytotoxic T lymphocyte antigen 4 (CTLA-4) in Treg cells via the Ca²⁺ transporter ATP2a3. This in turn inhibited macrophage reactive oxygen species production and promoted Mtb survival inside macrophages. Rv1272c-induced linoleic acid further promoted Mtb immune evasion by increasing CTLA-4 surface trafficking on Treg cells in vivo. Mechanistically, linoleic acid interacts with ATP2a3 in Treg cells and promotes mitochondria-associated endoplasmic reticulum (ER) membrane formation. This facilitates ER-to-mitochondria Ca2+ transfer and depletion of Ca2+ in the ER, and triggers store-operated calcium entry, thus elevating cytosolic Ca2+ levels to increase Ca2+-dependent CTLA-4 surface trafficking in Treg cells. These findings reveal that Mtb can use a metabolite to manipulate host responses and promote its intracellular survival.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"39 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261282","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 gut bacteria produce structurally related monoglycolipids with contrasting immune functions.","authors":"Ji-Sun Yoo,Da-Jung Jung,Byoungsook Goh,Kyoo Heo,Wen Zheng,ChangWon C Lee,Jeong In Seo,Naama Geva-Zatorsky,Meng Wu,Seung Bum Park,Dennis L Kasper,Sungwhan F Oh","doi":"10.1038/s41564-025-02141-1","DOIUrl":"https://doi.org/10.1038/s41564-025-02141-1","url":null,"abstract":"Gut symbiont Bacteroides fragilis can produce α-galactosylceramides (BfaGCs), sphingolipids with immunomodulatory functions that regulate colonic natural killer T (NKT) cells. However, their synthesis pathway and whether other human gut bacteria can produce them are unclear. Here, using genetic and metabolomic approaches, we mapped the sphingolipid biosynthesis pathway of B. fragilis and determined that α-galactosyltransferase (agcT) is essential and sufficient for colonic NKT cell regulation in mice. The distribution of agcT is restricted to only a few species among Bacteroidales. However, structural homologues of AgcT, such as BgsB, are widely distributed in gut microbiota and produce α-glycosyldiacylglycerols (aGDGs), particularly in Enterococcus. Analysis of infant gut metagenomes revealed that B. fragilis predominantly accounts for agcT abundance regardless of the cohort, but bgsB-encoding bacteria were taxonomically diverse and showed dynamic changes with host age. In addition, aGDGs from bgsB-encoding species act as antagonistic ligands for BfaGC-mediated NKT cell activation in vitro and in vivo. Our findings highlight the distinct natures of immunoactive glycolipid-producing symbionts and their relevance in the human gut microbiome, particularly in early life.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"86 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261284","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":"A generative artificial intelligence approach for the discovery of antimicrobial peptides against multidrug-resistant bacteria.","authors":"Yihui Wang,Lanlan Zhao,Ziyun Li,Yaxuan Xi,Yingmiao Pan,Guoping Zhao,Lei Zhang","doi":"10.1038/s41564-025-02114-4","DOIUrl":"https://doi.org/10.1038/s41564-025-02114-4","url":null,"abstract":"The discovery of novel antimicrobial peptides (AMPs) against clinical superbugs is urgently needed to address the ongoing antibiotic resistance crisis. AMPs are promising candidates due to their broad-spectrum activity, rapid bactericidal mechanisms and reduced likelihood of inducing resistance compared with conventional antibiotics. Here, a pre-trained protein large language model (LLM), ProteoGPT, was established and further developed into multiple specialized subLLMs to assemble a sequential pipeline. This pipeline enables rapid screening across hundreds of millions of peptide sequences, ensuring potent antimicrobial activity and minimizing cytotoxic risks. Through transfer learning, we endowed the LLMs with different domain-specific knowledge to achieve high-throughput mining and generation of AMPs within a unified methodological framework. Notably, both mined and generated AMPs exhibited reduced susceptibility to resistance development in ICU-derived carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA) in vitro. The AMPs also showed comparable or superior therapeutic efficacy in in vivo thigh infection mouse models compared with clinical antibiotics, without causing organ damage and disrupting gut microbiota. The mechanisms of action of these AMPs involve disruption of the cytoplasmic membrane and membrane depolarization. Overall, this study presents a generative artificial intelligence approach for the discovery of novel antimicrobials against multidrug-resistant bacteria, enabling efficient and extensive exploration of AMP space.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"8 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215941","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}