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Regulation of surface architecture by symbiotic bacteria mediates host colonization

Liu, Cui Hua and Lee, S. Melanie and VanLare, Jordan M. and Kasper, Dennis L. and Mazmanian, Sarkis K. (2008) Regulation of surface architecture by symbiotic bacteria mediates host colonization. Proceedings of the National Academy of Sciences of the United States of America, 105 (10). pp. 3951-3956. ISSN 0027-8424. PMCID PMC2268772. https://resolver.caltech.edu/CaltechAUTHORS:LIUpnas08

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PDF (Fig. 5. (A) Wild-type and CPM1 (Dmpi) strains display no aggregation... ) The autoaggregation phenotype of day-1 CPM2 liquid culture ...) - Supplemental Material
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PDF (Fig. 6. Transcriptional reporter assay shows that invertible promoters do not possess activity when locked in the "off" orientation.) - Supplemental Material
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PDF (Fig. 7. EtBr-stained agarose gel electrophoresis analysis of the PSB invertible promoter region from CPM1 and CPM3 chromosomal DNA is amplified with PCR using primers B1 and B5 (SI Table 1).) - Supplemental Material
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PDF (Fig. 8. Flow cytometry analysis of surface polysaccharides shows PSC expression in >70% of bacterial cells after the specific mutation of only the psb locus (B. fragilis 9343DPSB) but in only 4.2% of wild-type cultured cells (Fig. 1D).) - Supplemental Material
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PDF (Fig. 9. PCR analysis of the reporter plasmids containing one of the six invertible capsular polysaccharide promoters (psa, psd, pse, psf, psg, and psh) in the "off" orientation. Upon introduction into bacteria, all six of the "off"-oriented invertible ...) - Supplemental Material
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PDF (Fig. 10. EtBr-stained agarose gel electrophoresis of PCR products generated from chromosomal DNA of B. fragilis mutant CPM3 (Dmpi, Dpsc) complemented with ssr3 gene (CPM3 pFD340-ssr3) with specific primers for both the "on" and the "off" orientations ...) - Supplemental Material
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PDF (Fig. 10. EtBr-stained agarose gel electrophoresis of PCR products generated from chromosomal DNA of B. fragilis mutant CPM3 (Dmpi, Dpsc) complemented with ssr3 gene (CPM3 pFD340-ssr3) with specific primers for both the "on" and the "off" orientations ...) - Supplemental Material
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PDF (Fig. 12. CPM3 (expressing only PSB) is outcompeted by wild-type bacteria in animal colonization but displays no in vitro growth defect in co-culture with wild-type strain.) - Supplemental Material
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Abstract

Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host–symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the bacterial capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in capsule expression. Surprisingly, attempts to completely eliminate capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host–symbiont mutualism.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0709266105DOIArticle
http://www.pnas.org/content/105/10/3951.abstractPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268772/PubMed CentralArticle
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2008 by the National Academy of Sciences. Edited by Rino Rappuoli, Novartis Vaccines, Siena, Italy, and approved January 10, 2008 (received for review October 4, 2007). Published online before print March 4, 2008. We are very grateful to Dr. Laurie Comstock (Brigham and Women’s Hospital, Harvard Medical School, Boston) for helpful discussions and reagents throughout the entire course of this work, and we thank the members of the S.K.M. laboratory for comments on the manuscript. D.L.K. acknowledges support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. S.K.M. acknowledges support from the Searle Scholars Program and the Crohn’s and Colitis Foundation of America.
Funders:
Funding AgencyGrant Number
Searle Scholars ProgramUNSPECIFIED
National Institute of Allergy and Infectious DiseasesUNSPECIFIED
Crohn’s and Colitis Foundation of AmericaUNSPECIFIED
Subject Keywords:bacterial symbiosis; Bacteroides fragilis; capsular polysaccharide; intestinal microbiota
Issue or Number:10
PubMed Central ID:PMC2268772
Record Number:CaltechAUTHORS:LIUpnas08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:LIUpnas08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11215
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:26 Jul 2008 01:22
Last Modified:03 Oct 2019 00:16

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