Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.005
Aryan Rahimi-Midani, Igor Iatsenko
Symbiotic gut bacteria have evolved mechanisms to selectively recognize and colonize an appropriate host. In a recent issue of Science, Gutiérrez-García et al. reported a colonization island that encodes sugar-binding adhesins used by Lactiplantibacillus plantarum to colonize its symbiotic niche in the foregut of its host, Drosophila melanogaster.
{"title":"Colonization island directs L. plantarum to its niche","authors":"Aryan Rahimi-Midani, Igor Iatsenko","doi":"10.1016/j.chom.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.005","url":null,"abstract":"Symbiotic gut bacteria have evolved mechanisms to selectively recognize and colonize an appropriate host. In a recent issue of <em>Science</em>, Gutiérrez-García et al. reported a colonization island that encodes sugar-binding adhesins used by <em>Lactiplantibacillus plantarum</em> to colonize its symbiotic niche in the foregut of its host, <em>Drosophila melanogaster</em>.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"42 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393299","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}
Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.010
Liang Wang, George F. Gao
The H5 subtype of avian influenza viruses (AIVs) presents a continued threat to human health, intensifying with the H5N1 outbreak in cattle herds and onward transmission to humans. In this commentary, we offer a brief history of and explore recent advances in H5Ny AIVs and their impact on public health.
{"title":"A brief history of human infections with H5Ny avian influenza viruses","authors":"Liang Wang, George F. Gao","doi":"10.1016/j.chom.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.010","url":null,"abstract":"The H5 subtype of avian influenza viruses (AIVs) presents a continued threat to human health, intensifying with the H5N1 outbreak in cattle herds and onward transmission to humans. In this commentary, we offer a brief history of and explore recent advances in H5Ny AIVs and their impact on public health.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"16 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393304","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}
Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.003
Mingxi Li, Dapeng Li
In this issue of Cell Host & Microbe, Hesselman et al. investigate the relationship between the presence of non-canonical cysteine residues in HIV-1 V1 region of the Envelope glycoprotein and the development of neutralization breadth through population-based analyses.
{"title":"Cysteines shape antibody battles for HIV-1 Env","authors":"Mingxi Li, Dapeng Li","doi":"10.1016/j.chom.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.003","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Hesselman et al. investigate the relationship between the presence of non-canonical cysteine residues in HIV-1 V1 region of the Envelope glycoprotein and the development of neutralization breadth through population-based analyses.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"65 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393301","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}
Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.007
Nonhlanhla Lunjani, Liam O’Mahony
Two recent studies by Gribonika et al. and Bousbaine et al., published in Nature, describe the mechanisms underpinning skin autonomous B cell antibody responses to skin microbes and the immunodominant antibody target in Staphylococcus epidermidis that can be utilized to engineer novel topical vaccination strategies.
{"title":"Skin-deep immune sensing","authors":"Nonhlanhla Lunjani, Liam O’Mahony","doi":"10.1016/j.chom.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.007","url":null,"abstract":"Two recent studies by Gribonika et al. and Bousbaine et al., published in <em>Nature</em>, describe the mechanisms underpinning skin autonomous B cell antibody responses to skin microbes and the immunodominant antibody target in <em>Staphylococcus epidermidis</em> that can be utilized to engineer novel topical vaccination strategies.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"41 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393919","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}
Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.009
Fabian Wittmers, Camille Poirier, Charles Bachy, Charlotte Eckmann, Olga Matantseva, Craig A. Carlson, Stephen J. Giovannoni, Ursula Goodenough, Alexandra Z. Worden
Protists are major predators of ocean microbial life, with an ancient history of entanglements with prokaryotes, but their delicate cell structures and recalcitrance to culturing hinder exploration of marine symbioses. We report that tiny oceanic protistan predators, specifically choanoflagellates—the closest living unicellular relatives of animals—and uncultivated MAST-3 form symbioses with four bacterial lineages related to animal symbionts. By targeting living phagotrophs on ship expeditions, we recovered genomes from physically associated uncultivated Legionellales and Rickettsiales. The evolutionary trajectories of Marinicoxiellaceae, Cosmosymbacterales, Simplirickettsiaceae, and previously named Gamibacteraceae vary, including host-engagement mechanisms unknown in marine bacteria, horizontally transferred genes that mediate pathogen-microbiome interactions, and nutritional pathways. These symbionts and hosts occur throughout subtropical and tropical oceans. Related bacteria were detected in public data from freshwater, fish, and human samples. Symbiont associations with animal-related protists, alongside relationships to animal pathogens, suggest an unexpectedly long history of shifting associations and possibilities for host expansion as environments change.
{"title":"Symbionts of predatory protists are widespread in the oceans and related to animal pathogens","authors":"Fabian Wittmers, Camille Poirier, Charles Bachy, Charlotte Eckmann, Olga Matantseva, Craig A. Carlson, Stephen J. Giovannoni, Ursula Goodenough, Alexandra Z. Worden","doi":"10.1016/j.chom.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.009","url":null,"abstract":"Protists are major predators of ocean microbial life, with an ancient history of entanglements with prokaryotes, but their delicate cell structures and recalcitrance to culturing hinder exploration of marine symbioses. We report that tiny oceanic protistan predators, specifically choanoflagellates—the closest living unicellular relatives of animals—and uncultivated MAST-3 form symbioses with four bacterial lineages related to animal symbionts. By targeting living phagotrophs on ship expeditions, we recovered genomes from physically associated uncultivated Legionellales and Rickettsiales. The evolutionary trajectories of Marinicoxiellaceae, Cosmosymbacterales, Simplirickettsiaceae, and previously named Gamibacteraceae vary, including host-engagement mechanisms unknown in marine bacteria, horizontally transferred genes that mediate pathogen-microbiome interactions, and nutritional pathways. These symbionts and hosts occur throughout subtropical and tropical oceans. Related bacteria were detected in public data from freshwater, fish, and human samples. Symbiont associations with animal-related protists, alongside relationships to animal pathogens, suggest an unexpectedly long history of shifting associations and possibilities for host expansion as environments change.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"22 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393354","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}
Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.006
Xinglou Yang, Sandra Chiu
Receptor binding is the first step for virus infection. In this issue of Cell Host & Microbe, Gorka et al. conducted large-scale receptor binding assays with machine learning to predict susceptible host species and guide proactive filovirus surveillance. This study provides multidisciplinary blueprints for research and prevention of zoonotic disease.
{"title":"Accelerating mammalian filovirus research with receptor binding blueprints","authors":"Xinglou Yang, Sandra Chiu","doi":"10.1016/j.chom.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.006","url":null,"abstract":"Receptor binding is the first step for virus infection. In this issue of <em>Cell Host & Microbe</em>, Gorka et al. conducted large-scale receptor binding assays with machine learning to predict susceptible host species and guide proactive filovirus surveillance. This study provides multidisciplinary blueprints for research and prevention of zoonotic disease.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"50 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393303","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}
Pub Date : 2025-02-12DOI: 10.1016/j.chom.2025.01.002
Moamen M. Elmassry, Kohei Sugihara, Pranatchareeya Chankhamjon, Yeji Kim, Francine R. Camacho, Shuo Wang, Yuki Sugimoto, Seema Chatterjee, Lea Ann Chen, Nobuhiko Kamada, Mohamed S. Donia
Gut microbiome changes have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a meta-analysis of small molecule biosynthetic gene clusters (BGCs) in metagenomic samples of the gut microbiome from inflammatory bowel disease (IBD) patients and matched healthy subjects and identified two Clostridia-derived BGCs that are significantly associated with Crohn’s disease (CD), a main IBD type. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the CD-enriched BGCs, which we subsequently detected in fecal samples from IBD patients. Finally, we show that the discovered molecules disrupt gut permeability and exacerbate disease in chemically or genetically susceptible mouse models of colitis. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of disease-relevant microbiome-host interactions.
{"title":"A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules","authors":"Moamen M. Elmassry, Kohei Sugihara, Pranatchareeya Chankhamjon, Yeji Kim, Francine R. Camacho, Shuo Wang, Yuki Sugimoto, Seema Chatterjee, Lea Ann Chen, Nobuhiko Kamada, Mohamed S. Donia","doi":"10.1016/j.chom.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.002","url":null,"abstract":"Gut microbiome changes have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a meta-analysis of small molecule biosynthetic gene clusters (BGCs) in metagenomic samples of the gut microbiome from inflammatory bowel disease (IBD) patients and matched healthy subjects and identified two Clostridia-derived BGCs that are significantly associated with Crohn’s disease (CD), a main IBD type. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the CD-enriched BGCs, which we subsequently detected in fecal samples from IBD patients. Finally, we show that the discovered molecules disrupt gut permeability and exacerbate disease in chemically or genetically susceptible mouse models of colitis. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of disease-relevant microbiome-host interactions.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"129 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393356","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}
Pub Date : 2025-02-04DOI: 10.1016/j.chom.2025.01.008
Bentley Lim, Jinghua Xu, Igor H. Wierzbicki, Carlos G. Gonzalez, Zhe Chen, David J. Gonzalez, Xiang Gao, Andrew L. Goodman
Antagonistic interactions play a key role in determining microbial community dynamics. Here, we report that one of the most widespread contact-dependent effectors in human gut microbiomes, Bte1, directly targets the PpiD-YfgM periplasmic chaperone complex in related microbes. Structural, biochemical, and genetic characterization of this interaction reveals that Bte1 reverses the activity of the chaperone complex, promoting substrate aggregation and toxicity. Using Bacteroides, we show that Bte1 is active in the mammalian gut, conferring a fitness advantage to expressing strains. Recipient cells targeted by Bte1 exhibit sensitivity to membrane-compromising conditions, and human gut microbes can use this effector to exploit pathogen-induced inflammation in the gut. Further, Bte1 allelic variation in gut metagenomes provides evidence for an arms race between Bte1-encoding and immunity-encoding strains in humans. Together, these studies demonstrate that human gut microbes alter the protein-folding capacity of neighboring cells and suggest strategies for manipulating community dynamics.
{"title":"A human gut bacterium antagonizes neighboring bacteria by altering their protein-folding ability","authors":"Bentley Lim, Jinghua Xu, Igor H. Wierzbicki, Carlos G. Gonzalez, Zhe Chen, David J. Gonzalez, Xiang Gao, Andrew L. Goodman","doi":"10.1016/j.chom.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.008","url":null,"abstract":"Antagonistic interactions play a key role in determining microbial community dynamics. Here, we report that one of the most widespread contact-dependent effectors in human gut microbiomes, Bte1, directly targets the PpiD-YfgM periplasmic chaperone complex in related microbes. Structural, biochemical, and genetic characterization of this interaction reveals that Bte1 reverses the activity of the chaperone complex, promoting substrate aggregation and toxicity. Using <em>Bacteroides</em>, we show that Bte1 is active in the mammalian gut, conferring a fitness advantage to expressing strains. Recipient cells targeted by Bte1 exhibit sensitivity to membrane-compromising conditions, and human gut microbes can use this effector to exploit pathogen-induced inflammation in the gut. Further, Bte1 allelic variation in gut metagenomes provides evidence for an arms race between Bte1-encoding and immunity-encoding strains in humans. Together, these studies demonstrate that human gut microbes alter the protein-folding capacity of neighboring cells and suggest strategies for manipulating community dynamics.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"39 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083564","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}
Pub Date : 2025-02-04DOI: 10.1016/j.chom.2025.01.004
Maria C. Hesselman, Marius Zeeb, Peter Rusert, Chloé Pasin, Jennifer Mamrosh, Samuel Kariuki, Ian Pichler, Michèle Sickmann, Masako M. Kaufmann, Daniel Schmidt, Nikolas Friedrich, Karin J. Metzner, Audrey Rindler, Herbert Kuster, Craig Adams, Ruwayhida Thebus, Michael Huber, Sabine Yerly, Karoline Leuzinger, Matthieu Perreau, Alexandra Trkola
Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth. Analyzing over 65,000 V1 sequences from the CATNAP database, AMP trials, and longitudinal HIV-1 cohorts (SHCS, ZPHI, and CAPRISA), we found that Env variants with extra V1 Cys are present at low levels and fluctuate over time. Extra V1 Cys associate with elite plasma neutralization, and two additional Cys are preferred, suggesting stabilization through disulfide bonds. Among 34 broadly neutralizing antibody (bnAb)-inducer Envs, 17.6% had elongated V1 regions with extra Cys. These extra Cys moderately increased neutralization resistance and altered bnAb epitope accessibility. Collectively, altering epitope exposure alongside Env stabilization renders the V1 twin Cys motif a promising feature for HIV-1 bnAb immunogens.
{"title":"Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development","authors":"Maria C. Hesselman, Marius Zeeb, Peter Rusert, Chloé Pasin, Jennifer Mamrosh, Samuel Kariuki, Ian Pichler, Michèle Sickmann, Masako M. Kaufmann, Daniel Schmidt, Nikolas Friedrich, Karin J. Metzner, Audrey Rindler, Herbert Kuster, Craig Adams, Ruwayhida Thebus, Michael Huber, Sabine Yerly, Karoline Leuzinger, Matthieu Perreau, Alexandra Trkola","doi":"10.1016/j.chom.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.004","url":null,"abstract":"Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth. Analyzing over 65,000 V1 sequences from the CATNAP database, AMP trials, and longitudinal HIV-1 cohorts (SHCS, ZPHI, and CAPRISA), we found that Env variants with extra V1 Cys are present at low levels and fluctuate over time. Extra V1 Cys associate with elite plasma neutralization, and two additional Cys are preferred, suggesting stabilization through disulfide bonds. Among 34 broadly neutralizing antibody (bnAb)-inducer Envs, 17.6% had elongated V1 regions with extra Cys. These extra Cys moderately increased neutralization resistance and altered bnAb epitope accessibility. Collectively, altering epitope exposure alongside Env stabilization renders the V1 twin Cys motif a promising feature for HIV-1 bnAb immunogens.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"19 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083565","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}
Pub Date : 2025-01-29DOI: 10.1016/j.chom.2025.01.001
David J. Williams, Alexandra Hawkins, Ruth E. Hernandez, Giuseppina Mariano, Katharine Mathers, Grant Buchanan, Barnaby J. Stonier, Teresa Inkster, Alistair Leanord, James D. Chalmers, Nicholas R. Thomson, Matthew T.G. Holden, Sarah J. Coulthurst
Opportunistic bacterial pathogens must compete with other bacteria and switch between host- and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in gram-negative bacteria and can efficiently kill neighboring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly conserved antibacterial T6SS is differentially active between closely related clinical isolates of Serratia marcescens. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in S. marcescens isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility, and adhesion, with loss of BetR increasing virulence in an in vivo infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behavior, which is subject to selection pressure in clinical environments.
{"title":"Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment","authors":"David J. Williams, Alexandra Hawkins, Ruth E. Hernandez, Giuseppina Mariano, Katharine Mathers, Grant Buchanan, Barnaby J. Stonier, Teresa Inkster, Alistair Leanord, James D. Chalmers, Nicholas R. Thomson, Matthew T.G. Holden, Sarah J. Coulthurst","doi":"10.1016/j.chom.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.001","url":null,"abstract":"Opportunistic bacterial pathogens must compete with other bacteria and switch between host- and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in gram-negative bacteria and can efficiently kill neighboring competitors. We determined the distribution of T6SSs across the genus <em>Serratia</em> and observed that a highly conserved antibacterial T6SS is differentially active between closely related clinical isolates of <em>Serratia marcescens</em>. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in <em>S. marcescens</em> isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility, and adhesion, with loss of BetR increasing virulence in an <em>in vivo</em> infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behavior, which is subject to selection pressure in clinical environments.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"32 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055385","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}
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