Cell host & microbe最新文献

A phage-encoded small RNA that mimics chimeric guide to inhibit CRISPR-Cas9 一种噬菌体编码的小RNA，模仿嵌合向导抑制CRISPR-Cas9

IF 30.3 1区医学

Cell host & microbe Pub Date : 2026-10-21 DOI: 10.1016/j.chom.2026.09.017

Ying Chen,Peng Zhao,Chenmin Guo,Dandan Chen,Caihong Yun,Jiyun Chen,Liang Liu

{"title":"A phage-encoded small RNA that mimics chimeric guide to inhibit CRISPR-Cas9","authors":"Ying Chen,Peng Zhao,Chenmin Guo,Dandan Chen,Caihong Yun,Jiyun Chen,Liang Liu","doi":"10.1016/j.chom.2026.09.017","DOIUrl":"https://doi.org/10.1016/j.chom.2026.09.017","url":null,"abstract":"CRISPR-Cas9 relies on a dual CRISPR RNA (crRNA)-trans-activating crRNA (tracrRNA) guide, yet whether RNA-based anti-CRISPRs exist for this system has remained unknown. Here, we identify a phage-encoded small non-coding RNA, rAcrIIA1, that adopts an unexpected chimeric crRNA-tracrRNA architecture, faithfully recapitulating the entire single-guide RNA (sgRNA) of Cas9. Cryo-electron microscopy (cryo-EM) structures of the Cas9-rAcrIIA1 binary complex and the Cas9-rAcrIIA1-DNA ternary complex reveal that rAcrIIA1 engages Cas9 nearly identically to the native sgRNA, competitively blocking crRNA and tracrRNA loading and thereby abolishing DNA interference. Strikingly, beyond its natural inhibitory function, rAcrIIA1 is fully reprogrammable: with variable guide sequences, it directs Cas9 for sequence-specific DNA cleavage with efficiency comparable to the canonical sgRNA, and it activates trans-cleavage more potently. Thus, rAcrIIA1 provides an experimentally validated, mechanistically resolved RNA-based inhibitor of CRISPR-Cas9, reveals a distinct anti-CRISPR mechanism through complete sgRNA mimicry, and serves as a versatile bifunctional scaffold for genome editing and diagnostics.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"12 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of phage defense systems through component modularity networks 通过组件模块化网络发现噬菌体防御系统

IF 30.3 1区医学

Cell host & microbe Pub Date : 2026-10-20 DOI: 10.1016/j.chom.2026.09.018

Daan F. van den Berg,Ana Rita Costa,Jelger Q. Esser,Aswin Muralidharan,Halewijn van den Bossche,Desi Fierlier,Alexey Fomenkov,Ruoyue Wu,Jiangbo Wei,Peter R. Weigele,Liang Cui,Stan J.J. Brouns

{"title":"Discovery of phage defense systems through component modularity networks","authors":"Daan F. van den Berg,Ana Rita Costa,Jelger Q. Esser,Aswin Muralidharan,Halewijn van den Bossche,Desi Fierlier,Alexey Fomenkov,Ruoyue Wu,Jiangbo Wei,Peter R. Weigele,Liang Cui,Stan J.J. Brouns","doi":"10.1016/j.chom.2026.09.018","DOIUrl":"https://doi.org/10.1016/j.chom.2026.09.018","url":null,"abstract":"Phage defense systems in bacteria exhibit high degrees of modularity, with sensing, signal transmission, and effector enzymes frequently exchanged among phage defense gene clusters. In this study, we capitalize on this modularity to discover phage defense systems by searching for defense-associated modules in new gene contexts across Pseudomonas aeruginosa genomes. This approach reveals a large and interconnected network of modular components distributed across diverse gene clusters. From over 500 candidate defense systems, we select five for experimental testing and validate three: Dionysus, a TerB-encoding system that interferes with early phage infection (EPI) vesicle formation by jumbo phages; Ophion, a radical S-adenosyl-L-methionine (SAM)-containing system that blocks progression from the EPI vesicle to the nucleus stage during jumbo phage infection; and Hercules, a tightly regulated restriction-modification (RM)-like system. Collectively, we demonstrate that leveraging the modular architecture of phage defense systems is an effective approach to their discovery.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"37 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Akkermansia muciniphila protects against endometritis through a tyrosol-mediated gut-uterus axis 嗜粘阿克曼氏菌通过酪氨酸介导的肠-子宫轴保护子宫内膜炎

IF 30.3 1区医学

Cell host & microbe Pub Date : 2026-10-15 DOI: 10.1016/j.chom.2026.09.012

Linkai Qu,Jiapei Cai,Xinyu Zhang,Yuhang He,Jiuxi Liu,Xufeng Xie,Yongguo Cao

{"title":"Akkermansia muciniphila protects against endometritis through a tyrosol-mediated gut-uterus axis","authors":"Linkai Qu,Jiapei Cai,Xinyu Zhang,Yuhang He,Jiuxi Liu,Xufeng Xie,Yongguo Cao","doi":"10.1016/j.chom.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.chom.2026.09.012","url":null,"abstract":"Endometritis is a common reproductive disorder in humans and domestic animals that causes infertility and livestock losses. However, few specific bacteria and related metabolites involved in its pathogenesis have been identified. Here, we find that endometritis cows (EC) exhibit gut dysbiosis, with depletion of Akkermansia muciniphila (AKK). Gut microbiota transplantation from EC (E-GMT) induces endometritis in mice, whereas gut microbiota transplantation from healthy cows (H-GMT) does not. Supplementation with live AKK or its culture supernatant, but not heat-inactivated AKK, alleviates Escherichia coli-induced endometritis and protects E-GMT mice. Metabolomic profiling shows that live AKK increases tyrosol levels. Genomic and functional analyses support a role for AKK-derived alcohol dehydrogenase (ADH)1/ADH2 in tyrosol production. Engineered bacteria overexpressing this enzyme reproduce the anti-endometritis effects, whereas enzyme inhibition abolishes AKK-mediated protection. Mechanistically, tyrosol exerts protective effects by activating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway via upregulation of SIRT1 expression, highlighting the gut-uterine axis as a target for endometritis and uterine diseases.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"48 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gemella morbillorum promotes colorectal tumorigenesis through barrier disruption and invasion-dependent DNA damage morbillorum通过屏障破坏和侵袭依赖性DNA损伤促进结直肠肿瘤的发生

IF 30.3 1区医学

Cell host & microbe Pub Date : 2026-10-15 DOI: 10.1016/j.chom.2026.09.016

Marianne Meyers,Gabriel Medina Evora,Jose Alberto Molina Tijeras,Madita Brauer,Mohaned Benzarti,Maude Jans,Luis F. Delgado,Lena Schorr,Fabien Rodriguez,Dominik Ternes,Kyanna S. Ouyang,Kamil Moskal,Lisa Schlicker,Mina Tsenkova,Mara Lucchetti,Cedric Gilson,Monica Gabola,Anais Carpentier,Paolo G. Nuciforo,Eric Koncina,Vitaly I. Pozdeev,Lars Vereecke,Paul Wilmes,Jens Puschhof,Elisabeth Letellier

{"title":"Gemella morbillorum promotes colorectal tumorigenesis through barrier disruption and invasion-dependent DNA damage","authors":"Marianne Meyers,Gabriel Medina Evora,Jose Alberto Molina Tijeras,Madita Brauer,Mohaned Benzarti,Maude Jans,Luis F. Delgado,Lena Schorr,Fabien Rodriguez,Dominik Ternes,Kyanna S. Ouyang,Kamil Moskal,Lisa Schlicker,Mina Tsenkova,Mara Lucchetti,Cedric Gilson,Monica Gabola,Anais Carpentier,Paolo G. Nuciforo,Eric Koncina,Vitaly I. Pozdeev,Lars Vereecke,Paul Wilmes,Jens Puschhof,Elisabeth Letellier","doi":"10.1016/j.chom.2026.09.016","DOIUrl":"https://doi.org/10.1016/j.chom.2026.09.016","url":null,"abstract":"Bacteria are increasingly recognized as contributors to cancer, yet the underlying mechanisms remain unclear for most species. Here, we find that Gemella morbillorum (Gm) is enriched in feces and tumor tissues from patients with colorectal cancer (CRC) and reveal a multi-step host-pathogen mechanism that promotes colorectal tumorigenesis. In mouse models of CRC, Gm suppresses IL-22 production by type 3 innate lymphoid cells (ILC3s), impairing intestinal barrier function and facilitating bacterial translocation to early neoplastic lesions. At the tumor site, Gm utilizes an ANXA2-dependent, clathrin-mediated pathway to invade CRC cells. Gm induces profound lipid remodeling, characterized by the accumulation of oxidation-prone fatty acids and enhanced lipid peroxidation, which contributes to invasion-dependent DNA damage. Inhibition of lipid peroxidation attenuates Gm-induced DNA damage, functionally linking lipid oxidative stress to genotoxicity. Together, these findings identify Gm as a candidate onco-pathogen in CRC that uses multiple mechanisms to disarm the intestinal barrier and trigger genotoxicity.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"11 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pleiotropic roles of microbial bile acid metabolism in intestinal health and diseases 微生物胆汁酸代谢在肠道健康和疾病中的多效作用

IF 30.3 1区医学

Cell host & microbe Pub Date : 2026-10-14 DOI: 10.1016/j.chom.2026.09.010

Ming Qi,Xiaoyan Liu,Frank J. Gonzalez

引用次数: 0

Mutant KRAS favors a microbe that signals back 突变的KRAS倾向于一种能发出回信号的微生物

IF 30.3 1区医学

Cell host & microbe Pub Date : 2026-10-14 DOI: 10.1016/j.chom.2026.09.007

Na Jiao,Lixin Zhu,Ruixin Zhu

引用次数: 0

Encrypting the message: Bacterium turns host RNA into a target 加密信息：细菌将宿主RNA变成目标