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Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo

We recently showed that human gut Bacteroidales species secrete antimicrobial proteins (BSAPs), and we characterized in vitro the first such BSAP produced by Bacteroides fragilis. In this study, we identified a second potent BSAP produced by the ubiquitous and abundant human gut species Bacteroides...

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Autores principales: Roelofs, Kevin G., Coyne, Michael J., Gentyala, Rahul R., Chatzidaki-Livanis, Maria, Comstock, Laurie E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999547/
https://www.ncbi.nlm.nih.gov/pubmed/27555309
http://dx.doi.org/10.1128/mBio.01055-16
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author Roelofs, Kevin G.
Coyne, Michael J.
Gentyala, Rahul R.
Chatzidaki-Livanis, Maria
Comstock, Laurie E.
author_facet Roelofs, Kevin G.
Coyne, Michael J.
Gentyala, Rahul R.
Chatzidaki-Livanis, Maria
Comstock, Laurie E.
author_sort Roelofs, Kevin G.
collection PubMed
description We recently showed that human gut Bacteroidales species secrete antimicrobial proteins (BSAPs), and we characterized in vitro the first such BSAP produced by Bacteroides fragilis. In this study, we identified a second potent BSAP produced by the ubiquitous and abundant human gut species Bacteroides uniformis. The two BSAPs contain a membrane attack complex/perforin (MACPF) domain but share very little sequence similarity. We identified the target molecules of BSAP-sensitive cells and showed that each BSAP targets a different class of surface molecule: BSAP-1 targets an outer membrane protein of sensitive B. fragilis strains, and BSAP-2 targets the O-antigen glycan of lipopolysaccharide (LPS) of sensitive B. uniformis strains. Species-wide genomic and phenotypic analyses of B. fragilis and B. uniformis showed that BSAP-producing strains circumvent killing by synthesizing an orthologous nontargeted surface molecule. The BSAP genes are adjacent to the gene(s) encoding their target replacements, suggesting coacquisition. Using a gnotobiotic mouse competitive-colonization model, we found that the BSAP surface targets are important for colonization of the mammalian gut, thereby explaining why they are maintained in sensitive strains and why they were replaced rather than deleted in BSAP-producing strains. Using isogenic BSAP-producing, -sensitive, and -resistant strains, we show that a BSAP-producing strain outcompetes a sensitive strain but not a resistant strain in the mammalian gut. Human gut metagenomic datasets reveal that BSAP-1-sensitive strains do not cooccur with BSAP-1-producing strains in human gut microbiotas, further supporting the idea that BSAPs are important competitive factors with relevance to the strain-level composition of the human gut microbiota.
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spelling pubmed-49995472016-08-26 Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo Roelofs, Kevin G. Coyne, Michael J. Gentyala, Rahul R. Chatzidaki-Livanis, Maria Comstock, Laurie E. mBio Research Article We recently showed that human gut Bacteroidales species secrete antimicrobial proteins (BSAPs), and we characterized in vitro the first such BSAP produced by Bacteroides fragilis. In this study, we identified a second potent BSAP produced by the ubiquitous and abundant human gut species Bacteroides uniformis. The two BSAPs contain a membrane attack complex/perforin (MACPF) domain but share very little sequence similarity. We identified the target molecules of BSAP-sensitive cells and showed that each BSAP targets a different class of surface molecule: BSAP-1 targets an outer membrane protein of sensitive B. fragilis strains, and BSAP-2 targets the O-antigen glycan of lipopolysaccharide (LPS) of sensitive B. uniformis strains. Species-wide genomic and phenotypic analyses of B. fragilis and B. uniformis showed that BSAP-producing strains circumvent killing by synthesizing an orthologous nontargeted surface molecule. The BSAP genes are adjacent to the gene(s) encoding their target replacements, suggesting coacquisition. Using a gnotobiotic mouse competitive-colonization model, we found that the BSAP surface targets are important for colonization of the mammalian gut, thereby explaining why they are maintained in sensitive strains and why they were replaced rather than deleted in BSAP-producing strains. Using isogenic BSAP-producing, -sensitive, and -resistant strains, we show that a BSAP-producing strain outcompetes a sensitive strain but not a resistant strain in the mammalian gut. Human gut metagenomic datasets reveal that BSAP-1-sensitive strains do not cooccur with BSAP-1-producing strains in human gut microbiotas, further supporting the idea that BSAPs are important competitive factors with relevance to the strain-level composition of the human gut microbiota. American Society for Microbiology 2016-08-23 /pmc/articles/PMC4999547/ /pubmed/27555309 http://dx.doi.org/10.1128/mBio.01055-16 Text en Copyright © 2016 Roelofs et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Roelofs, Kevin G.
Coyne, Michael J.
Gentyala, Rahul R.
Chatzidaki-Livanis, Maria
Comstock, Laurie E.
Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo
title Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo
title_full Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo
title_fullStr Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo
title_full_unstemmed Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo
title_short Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo
title_sort bacteroidales secreted antimicrobial proteins target surface molecules necessary for gut colonization and mediate competition in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999547/
https://www.ncbi.nlm.nih.gov/pubmed/27555309
http://dx.doi.org/10.1128/mBio.01055-16
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