Structural and molecular insights into novel surface‐exposed mucus adhesins from Lactobacillus reuteri human strains. Issue 3 (2nd April 2014)

• Record Type: Journal Article
• Authors: Etzold, Sabrina; MacKenzie, Donald A.; Jeffers, Faye; Walshaw, John; Roos, Stefan; Hemmings, Andrew M.; Juge, Nathalie
• Is Part Of: Molecular microbiology. Volume 92:Issue 3(2014)
• Page Start: 543
• Page End: 556
• Publication Date: 2014-04-02
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12574
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The mucus layer covering the gastrointestinal tract is the first point of contact of the intestinal microbiota with the host. Cell surface macromolecules are critical for adherence of commensal bacteria to mucus but structural information is scarce. Here we report the first molecular and structural characterization of a novel cell‐surface protein, Lar_0958 from <italic>L</italic><italic>actobacillus reuteri</italic> JCM 1112<sup>T</sup>, mediating adhesion of <italic>L</italic><italic>. reuteri</italic> human strains to mucus. Lar_0958 is a modular protein of 133 kDa containing six repeat domains, an N‐terminal signal sequence and a C‐terminal anchoring motif (LPXTG). Lar_0958 homologues are expressed on the cell‐surface of <italic>L</italic><italic>. reuteri</italic> human strains, as shown by flow‐cytometry and immunogold microscopy. Adhesion of human <italic>L</italic><italic>. reuteri</italic> strains to mucus <italic>in vitro</italic> was significantly reduced in the presence of an anti‐Lar_0958 antibody and Lar_0958 contribution to adhesion was further confirmed using a <italic>L</italic><italic>. reuteri</italic> ATCC PTA 6475 <italic>lar_0958</italic> KO mutant (6475‐KO). The X‐ray crystal structure of a single Lar_0958 repeat, determined at 1.5 Å resolution, revealed a divergent immunoglobulin (Ig)‐like β‐sandwich fold, sharing structural homology with the Ig‐like inter‐repeat domain of internalins of the food borne pathogen <italic>L</italic><italic>isteria monocytogenes</italic>. These findings provide unique structural insights into cell‐surface protein repeats involved in adhesion of Gram‐positive bacteria to the intestine.</p> </abstract>