Daniele Albertini,Emanuel A. Devers,Gregory Schott,Rajendran Rajeswaran,Maëlle Jacquemettaz,Olivier Voinnet
{"title":"Mobile virus-derived siRNAs drive plant antiviral silencing through reiterated 3–4 cell immunization","authors":"Daniele Albertini,Emanuel A. Devers,Gregory Schott,Rajendran Rajeswaran,Maëlle Jacquemettaz,Olivier Voinnet","doi":"10.1016/j.chom.2026.08.005","DOIUrl":"https://doi.org/10.1016/j.chom.2026.08.005","url":null,"abstract":"The movement of virus-derived small interfering RNAs (vsiRNAs) between plant cells has prompted the widely held assumption that they help immunize as-yet-uninfected tissues. Ascertaining this role is challenging because it requires uncoupling vsiRNA mobility from viral movement while preserving viral virulence. Consequently, the contribution of non-cell-autonomous RNAi to plant antiviral immunity remains essentially unknown. Here, we investigate the naturally phloem-restricted infection of turnip yellows virus (TuYV) in the stereotypical Arabidopsis root system at cellular resolution. We uncover intertwined, complex mechanisms operating in both vsiRNA-emitting and -recipient cells, which drive reiterated short-range (∼3–4 cell) immunization events. We find that, while intracellular antiviral RNAi is essentially nullified by TuYV, non-cell-autonomous immunization by vsiRNAs accounts mainly—if not exclusively—for the containment of viral titers and tissue invasion at the whole-plant scale. Mobile vsiRNA-mediated immunization likewise spatially confines a TuYV-unrelated virus over ∼3–4 cells, uncovering a generic, essential, yet previously unrecognized component of plant antiviral defense.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"12 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877410","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}
{"title":"Dual sensing activates antiviral reverse transcriptase for membrane targeting","authors":"Yushan Xia,Hua Qi,Xin-Yang Wei,Jun-Tao Zhang,Wenao Hu,Yu-Jun Liu,Xin-Yi Song,Xue Liu,Chongyuan Wang,Ning Jia","doi":"10.1016/j.chom.2026.08.006","DOIUrl":"https://doi.org/10.1016/j.chom.2026.08.006","url":null,"abstract":"The prokaryotic type 2 defense-associated reverse transcriptase (DRT2) system mediates antiviral defense by catalyzing the rolling-circle reverse transcription of a noncoding RNA (ncRNA) and producing the toxic Neo protein that arrests bacterial growth. However, the mechanisms underlying DRT2 activation and effector function remain unknown. Here, we identified two distinct activation mechanisms: direct binding of a phage-encoded single-stranded DNA-binding protein (SSB or SSAP), and the detection of elevated intracellular dGTP levels induced by the phage-encoded ribonucleotide reductase NrdAB. Upon activation, the produced Neo protein directly targets the bacterial membrane, inducing membrane depolarization and growth arrest. Cryo-electron microscopy (cryo-EM) structures of the DRT2-ncRNA complex in its arrested and dGTP-bound active states provide mechanistic insights into rolling-circle ccDNA synthesis and template jumping. Furthermore, these identified activation mechanisms enable the DRT2 system with an engineered ncRNA template to produce a large-scale, user-defined double-stranded DNA (dsDNA) template in vivo, highlighting its potential in biotechnological applications.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"57 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877409","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}
Akihiko Oka,Gerold Bongers,Yoshiyuki Mishima,Andrew J. Baltus,Simon M. Gray,Bo Liu,Jeremy W. Herzog,John R. Benedetto,Ting-Jia Fan,Jisun Jang,Muyiwa Awoniyi,Esmat Rousta,Ling-Yang Hao,Raad Z. Gharaibeh,Anthony A. Fodor,Toshifumi Ohkusa,Koji Atarashi,Shinji Fukuda,Kenya Honda,Lani R. San Mateo,R. Balfour Sartor
{"title":"Defined human Clostridia consortia reverse colitis via dual effects of tryptophan metabolites on microbiota and immunity","authors":"Akihiko Oka,Gerold Bongers,Yoshiyuki Mishima,Andrew J. Baltus,Simon M. Gray,Bo Liu,Jeremy W. Herzog,John R. Benedetto,Ting-Jia Fan,Jisun Jang,Muyiwa Awoniyi,Esmat Rousta,Ling-Yang Hao,Raad Z. Gharaibeh,Anthony A. Fodor,Toshifumi Ohkusa,Koji Atarashi,Shinji Fukuda,Kenya Honda,Lani R. San Mateo,R. Balfour Sartor","doi":"10.1016/j.chom.2026.08.003","DOIUrl":"https://doi.org/10.1016/j.chom.2026.08.003","url":null,"abstract":"Microbial dysbiosis and disrupted mucosal immune homeostasis are integrally involved in the pathogenesis of inflammatory bowel diseases (IBDs). Live biotherapeutic products (LBPs) offer a potential therapeutic strategy to restore beneficial microbes and mitigate disease. We investigated the therapeutic efficacy of 2 LBPs, human Clostridia consortia 17-mix and 11-mix, by treating established colitis in murine models. Both LBPs exhibited therapeutic effects in T cell-mediated chronic colitis models induced by human microbiota and in pathobiont-driven gnotobiotic colitis models established with combinations of IBD-relevant human-derived strains. Metagenomic and metabolomic analyses elucidated mechanisms that go beyond established functions driven by short-chain fatty acids (SCFAs) and interleukin (IL)-10-producing regulatory T cells. Notably, LBPs exerted therapeutic effects by directly inhibiting resident pathobionts and through IL-10-independent activation of host anti-inflammatory aryl hydrocarbon receptor (AhR) pathways by bacterial tryptophan metabolites. These results elucidate SCFA- and IL-10-independent protective mechanisms exerted by defined resident bacterial strains that are depleted in IBD dysbiosis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"40 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148821630","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}
{"title":"Bacterial endosymbionts enhance fungal virulence by disrupting the disease-suppressive rhizobiome","authors":"Xingang Zhou,Xianhong Zhang,Lingyi Ran,Dongli Liu,Huiting Jia,Jingyu Zhang,Nan Zhang,Muhammad Khashi u Rahman,Alexandre Jousset,Francisco Dini-Andreote,Fengzhi Wu,Zhong Wei","doi":"10.1016/j.chom.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.chom.2026.08.001","url":null,"abstract":"The mechanisms by which bacterial endosymbionts (bacteria living within fungal cells) enhance the fitness and virulence of fungal pathogens remain poorly understood. Here, we report that the tomato Fusarium wilt pathogen Fusarium oxysporum f. sp. lycopersici (FOL) hosts Achromobacter spp. endosymbionts that enhance fungal virulence. This virulence potentiation is partially dependent on interactions with the native rhizosphere microbiota. We show that bacterial endosymbiont-harboring FOL reshapes the rhizosphere bacterial community during pathogen infection and decreases the abundance of disease-suppressive bacteria, including Streptomyces spp. taxa. This inhibitory effect is mediated by bacterial endosymbiont-stimulated production of beauvericin (an antibacterial cyclic hexadepsipeptide) by FOL. Together, our findings reveal a tripartite interaction in which a fungal pathogen leverages its bacterial endosymbiont to weaken rhizosphere microbiome-based disease suppression by inhibiting plant-protective bacterial taxa. This work highlights how cross-kingdom symbioses can modulate pathogen ecology and virulence in soil environments.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"6 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768875","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}
Kathleen McCaffrey,Stefan Gaussmann,Garrett Z. Ng,Tristan Dewald,Mark Helm,Frederic Allain,Elizabeth L. Hartland
{"title":"Bacterial effector modifies host messenger RNA to promote virulence","authors":"Kathleen McCaffrey,Stefan Gaussmann,Garrett Z. Ng,Tristan Dewald,Mark Helm,Frederic Allain,Elizabeth L. Hartland","doi":"10.1016/j.chom.2026.07.018","DOIUrl":"https://doi.org/10.1016/j.chom.2026.07.018","url":null,"abstract":"Bacterial pathogens harbor specialized secretion systems that inject effector proteins into the host cell to establish infection and disease. While many bacterial effectors post-translationally modify proteins to influence host responses, the extent to which effectors modify host RNA is currently unknown. Here we performed RNA-interactome capture (RIC) to isolate effectors bound to host cellular messenger RNA (mRNA) during Legionella pneumophila infection. RIC identified an uncharacterized effector, FadA (Lpw16921), which localized to the host-cell nucleus and interacted with host mRNAs at uracil (U)-rich RNA motifs. FadA exhibited NADPH-oxidase activity that mediated 8-oxo-guanine (oxo8G) modifications of mRNA substrates, resulting in oxidative damage and inhibition of translation. Infection with L. pneumophila harboring wild-type FadA, but not a catalytically inactive mutant, increased oxo8G modifications, suppressed cytokine responses, and promoted bacterial persistence in vivo. Our findings demonstrate the potential for a secreted effector to post-transcriptionally modify host mRNA as a mechanism to promote bacterial virulence.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"36 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768876","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}
Lae-Guen Jang,Ji-Won Huh,Seolah Kim,Ji-Young Lee,Hee-Soo Hwang,Jaekyung Yoon,Hyeon Gwon Lee,Tae Il Kim,Yong Chan Lee,Sun Ha Jee,Jihyun F. Kim
{"title":"Mouth-to-gut microbial transmission signatures enable robust, non-invasive diagnosis of gastrointestinal cancers","authors":"Lae-Guen Jang,Ji-Won Huh,Seolah Kim,Ji-Young Lee,Hee-Soo Hwang,Jaekyung Yoon,Hyeon Gwon Lee,Tae Il Kim,Yong Chan Lee,Sun Ha Jee,Jihyun F. Kim","doi":"10.1016/j.chom.2026.07.007","DOIUrl":"https://doi.org/10.1016/j.chom.2026.07.007","url":null,"abstract":"The human microbiome is spatially compartmentalized, yet oral bacteria can ectopically colonize distal sites such as the gut, potentially influencing disease. By analyzing paired oral and fecal microbiomes from 507 participants across healthy controls and patients with metabolic disorders or gastrointestinal cancers, we established a quantitative mouth-to-feces (MF) index to measure MF microbial transmission. The MF index revealed elevated mouth-to-gut transmission in cancer and a strong association with host metabolic and inflammatory indicators. Using transmitted taxa, we developed a random forest classifier that accurately distinguished gastric/colorectal cancer from healthy controls across seven independent cohorts, even when trained solely on oral microbiome data. When benchmarked against the conventional screening test, the MF-based model achieved markedly higher sensitivity than the fecal occult blood test. These findings uncover disease-specific transmission signatures and highlight MF microbial profiling as a generalizable, non-invasive framework for gastrointestinal cancer diagnosis and risk stratification.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"46 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768913","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}
Stefan A. Fattinger,Bianca Parisi,Roberto A. Chavez,Marian R. Fairgrieve,Ophelia V. Lee,Kristen C. Witt,Jesse J. Rodriguez,Elizabeth A. Turcotte,Ella C. Brydon,Harmandeep Dhaliwal,Angus Y. Lee,Dmitri I. Kotov,Russell E. Vance
{"title":"Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility","authors":"Stefan A. Fattinger,Bianca Parisi,Roberto A. Chavez,Marian R. Fairgrieve,Ophelia V. Lee,Kristen C. Witt,Jesse J. Rodriguez,Elizabeth A. Turcotte,Ella C. Brydon,Harmandeep Dhaliwal,Angus Y. Lee,Dmitri I. Kotov,Russell E. Vance","doi":"10.1016/j.chom.2026.07.014","DOIUrl":"https://doi.org/10.1016/j.chom.2026.07.014","url":null,"abstract":"Mycobacterium tuberculosis (Mtb) causes over one million deaths annually, but most infected individuals never exhibit symptoms. Type I interferons (IFNs) have emerged as a major factor driving susceptibility to Mtb, but how type I IFNs impair immunity to Mtb is a key unresolved question. Here, we show that an early effect of type I IFN during Mtb infection is the cell-intrinsic impairment of IFNγ signaling. IFNγ signaling is selectively impaired in the subset of infected macrophages experiencing high and sustained levels of type I IFN signaling. Genetic elimination of regulated stimulator of interferon via stabilization of transcript (RESIST), a recently described positive regulator of type I IFN production, specifically eliminates the high and sustained type I IFN response, fully restores IFNγ signaling, and rescues susceptibility to Mtb without affecting basal type I IFN responses. Our results demonstrate that strong and sustained type I IFN responses specifically and cell intrinsically impair responsiveness to IFNγ to cause susceptibility to Mtb.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148717825","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}
{"title":"Purging the transcriptome for antibiotic tolerance","authors":"João Pedro Teuber Carvalho, Daniel Schultz","doi":"10.1016/j.chom.2026.07.011","DOIUrl":"https://doi.org/10.1016/j.chom.2026.07.011","url":null,"abstract":"","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"63 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715640","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}