A Clostridium difficile Cell Wall Glycopolymer Locus Influences Bacterial Shape, Polysaccharide Production and Virulence
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Author
Chu, MicheleMallozzi, Michael J. G.
Roxas, Bryan P.

Bertolo, Lisa
Monteiro, Mario A.
Agellon, Al
Viswanathan, V. K.
Vedantam, Gayatri
Affiliation
Univ Arizona, Sch Anim & Comparat Biomed SciUniv Arizona, Dept Immunobiol, Inst Collaborat Res Bio5
Issue Date
2016-10-14
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PUBLIC LIBRARY SCIENCECitation
A Clostridium difficile Cell Wall Glycopolymer Locus Influences Bacterial Shape, Polysaccharide Production and Virulence 2016, 12 (10):e1005946 PLOS PathogensJournal
PLOS PathogensRights
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Clostridium difficile is a diarrheagenic pathogen associated with significant mortality and morbidity. While its glucosylating toxins are primary virulence determinants, there is increasing appreciation of important roles for non-toxin factors in C. difficile pathogenesis. Cell wall glycopolymers (CWGs) influence the virulence of various pathogens. Five C. difficile CWGs, including PSII, have been structurally characterized, but their biosynthesis and significance in C. difficile infection is unknown. We explored the contribution of a conserved CWG locus to C. difficile cell-surface integrity and virulence. Attempts at disrupting multiple genes in the locus, including one encoding a predicted CWG exporter mviN, were unsuccessful, suggesting essentiality of the respective gene products. However, antisense RNA-mediated mviN downregulation resulted in slight morphology defects, retarded growth, and decreased surface PSII deposition. Two other genes, lcpA and lcpB, with putative roles in CWG anchoring, could be disrupted by insertional inactivation. lcpA(-) and lcpB(-) mutants had distinct phenotypes, implying non-redundant roles for the respective proteins. The lcpB mutant was defective in surface PSII deposition and shedding, and exhibited a remodeled cell surface characterized by elongated and helical morphology, aberrantly-localized cell septae, and an altered surface-anchored protein profile. Both lcpA(-) and lcpB(-) strains also displayed heightened virulence in a hamster model of C. difficile disease. We propose that gene products of the C. difficile CWG locus are essential, that they direct the production/assembly of key antigenic surface polysaccharides, and thereby have complex roles in virulence.Note
Open Access Journal.ISSN
1553-7374Version
Final published versionSponsors
US Department of Veterans Affairs [1I01BX001183-01]; USDA CSREES Hatch Program [ARZT-570410-A-02-139]Additional Links
http://dx.plos.org/10.1371/journal.ppat.1005946ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1005946
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Except where otherwise noted, this item's license is described as This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.