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  • 1
    Publication Date: 2013-08-21
    Description: Mammals harbour a complex gut microbiome, comprising bacteria that confer immunological, metabolic and neurological benefits. Despite advances in sequence-based microbial profiling and myriad studies defining microbiome composition during health and disease, little is known about the molecular processes used by symbiotic bacteria to stably colonize the gastrointestinal tract. We sought to define how mammals assemble and maintain the Bacteroides, one of the most numerically prominent genera of the human microbiome. Here we find that, whereas the gut normally contains hundreds of bacterial species, germ-free mice mono-associated with a single Bacteroides species are resistant to colonization by the same, but not different, species. To identify bacterial mechanisms for species-specific saturable colonization, we devised an in vivo genetic screen and discovered a unique class of polysaccharide utilization loci that is conserved among intestinal Bacteroides. We named this genetic locus the commensal colonization factors (ccf). Deletion of the ccf genes in the model symbiont, Bacteroides fragilis, results in colonization defects in mice and reduced horizontal transmission. The ccf genes of B. fragilis are upregulated during gut colonization, preferentially at the colonic surface. When we visualize microbial biogeography within the colon, B. fragilis penetrates the colonic mucus and resides deep within crypt channels, whereas ccf mutants are defective in crypt association. Notably, the CCF system is required for B. fragilis colonization following microbiome disruption with Citrobacter rodentium infection or antibiotic treatment, suggesting that the niche within colonic crypts represents a reservoir for bacteria to maintain long-term colonization. These findings reveal that intestinal Bacteroides have evolved species-specific physical interactions with the host that mediate stable and resilient gut colonization, and the CCF system represents a novel molecular mechanism for symbiosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893107/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893107/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, S Melanie -- Donaldson, Gregory P -- Mikulski, Zbigniew -- Boyajian, Silva -- Ley, Klaus -- Mazmanian, Sarkis K -- DK078938/DK/NIDDK NIH HHS/ -- GM007616/GM/NIGMS NIH HHS/ -- GM099535/GM/NIGMS NIH HHS/ -- P01 DK091222/DK/NIDDK NIH HHS/ -- R01 DK078938/DK/NIDDK NIH HHS/ -- R01 GM099535/GM/NIGMS NIH HHS/ -- R21 DK083633/DK/NIDDK NIH HHS/ -- England -- Nature. 2013 Sep 19;501(7467):426-9. doi: 10.1038/nature12447. Epub 2013 Aug 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23955152" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacteroides/*classification/genetics/growth & development/*physiology ; Bacteroides fragilis/genetics/growth & development/metabolism ; Colon/microbiology ; Conserved Sequence/genetics ; Evolution, Molecular ; Female ; Gastrointestinal Tract/*microbiology ; Gene Deletion ; Genes, Bacterial/genetics ; Germ-Free Life ; Intestinal Mucosa/microbiology ; Male ; Metagenome/*physiology ; Mice ; Polysaccharides/metabolism ; Species Specificity ; Symbiosis/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2018-05-18
    Description: The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis.
    Keywords: Microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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