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Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Neff, C. Preston and Rhodes, Matthew E. and Arnolds, Kathleen L. and Collins, Colm B. and Donnelly, Jody and Nusbacher, Nichole and Jedlicka, Paul and Schneider, Jennifer M. and McCarter, Martin D. and Shaffer, Michael and Mazmanian, Sarkis K. and Palmer, Brent E. and Lozupone, Catherine A. (2016) Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties. Cell Host & Microbe, 20 (4). pp. 535-547. ISSN 1931-3128. PMCID PMC5113727. http://resolver.caltech.edu/CaltechAUTHORS:20161010-155756862

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Abstract

Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.chom.2016.09.002DOIArticle
http://www.sciencedirect.com/science/article/pii/S1931312816303791PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113727/PubMed CentralArticle
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2016 Elsevier. Received 18 November 2015; revised 19 July 2016; accepted 8 September 2016; available online 29 September 2016. We would like to thank Ashleigh Jones for her technical assistance with the mouse experiments. We would also like to express deep gratitude to Eric Martens for sharing with us the pKNOCK-bla-ermGb vector and for his guidance in conducting insertional transposon mutagenesis. This work was funded from R01 DK104047. C.A.L. was also supported by K01 DK090285. C.P.N. was supported by NIH T32 AI007405. C.B.C. was supported by K01 DK099403. S.K.M. is a co-founder of Symbiotix Biotherapies, which did not sponsor this work, nor is the company developing any potential technologies described here.
Funders:
Funding AgencyGrant Number
NIHR01 DK104047
NIHK01 DK090285
NIH Predoctoral FellowhsipT32 AI007405
NIHK01 DK099403
PubMed Central ID:PMC5113727
Record Number:CaltechAUTHORS:20161010-155756862
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20161010-155756862
Official Citation:C. Preston Neff, Matthew E. Rhodes, Kathleen L. Arnolds, Colm B. Collins, Jody Donnelly, Nichole Nusbacher, Paul Jedlicka, Jennifer M. Schneider, Martin D. McCarter, Michael Shaffer, Sarkis K. Mazmanian, Brent E. Palmer, Catherine A. Lozupone, Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties, Cell Host & Microbe, Volume 20, Issue 4, 12 October 2016, Pages 535-547, ISSN 1931-3128, http://dx.doi.org/10.1016/j.chom.2016.09.002. (http://www.sciencedirect.com/science/article/pii/S1931312816303791)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:70976
Collection:CaltechAUTHORS
Deposited By: Melissa Ray
Deposited On:11 Oct 2016 18:34
Last Modified:09 Jan 2017 21:01

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