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Title: Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development

Abstract

By combining X-ray crystallography and modelling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor-dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG-like domains, each of which harbours an intramolecular isopeptide bond, previously described in several Gram-positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell-cell interactions and biofilm formation, they contribute significantly to the proteolytic stability of FimA. Remarkably, FimA harbours two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram-positive fimbriae.

Authors:
; ; ; ; ; ; ; ;  [1];  [2];  [2];  [2]
  1. (Texas-HSC)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1024051
Resource Type:
Journal Article
Resource Relation:
Journal Name: Mol. Microbiol.; Journal Volume: 81; Journal Issue: (5) ; 09, 2011
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACTINOMYCES; ADHESIVES; CRYSTALLOGRAPHY; GENETICS; GLYCOPROTEINS; PLASMA; POLYSACCHARIDES; STABILITY; STAPHYLOCOCCUS

Citation Formats

Mishra, Arunima, Devarajan, Bharanidharan, Reardon, Melissa E., Dwivedi, Prabhat, Krishnan, Vengadesan, Cisar, John O., Das, Asis, Narayana, Sthanam V.L., Ton-That, Hung, NIH), UAB), and Connecticut). Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development. United States: N. p., 2011. Web. doi:10.1111/j.1365-2958.2011.07745.x.
Mishra, Arunima, Devarajan, Bharanidharan, Reardon, Melissa E., Dwivedi, Prabhat, Krishnan, Vengadesan, Cisar, John O., Das, Asis, Narayana, Sthanam V.L., Ton-That, Hung, NIH), UAB), & Connecticut). Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development. United States. doi:10.1111/j.1365-2958.2011.07745.x.
Mishra, Arunima, Devarajan, Bharanidharan, Reardon, Melissa E., Dwivedi, Prabhat, Krishnan, Vengadesan, Cisar, John O., Das, Asis, Narayana, Sthanam V.L., Ton-That, Hung, NIH), UAB), and Connecticut). 2011. "Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development". United States. doi:10.1111/j.1365-2958.2011.07745.x.
@article{osti_1024051,
title = {Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development},
author = {Mishra, Arunima and Devarajan, Bharanidharan and Reardon, Melissa E. and Dwivedi, Prabhat and Krishnan, Vengadesan and Cisar, John O. and Das, Asis and Narayana, Sthanam V.L. and Ton-That, Hung and NIH) and UAB) and Connecticut)},
abstractNote = {By combining X-ray crystallography and modelling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor-dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG-like domains, each of which harbours an intramolecular isopeptide bond, previously described in several Gram-positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell-cell interactions and biofilm formation, they contribute significantly to the proteolytic stability of FimA. Remarkably, FimA harbours two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram-positive fimbriae.},
doi = {10.1111/j.1365-2958.2011.07745.x},
journal = {Mol. Microbiol.},
number = (5) ; 09, 2011,
volume = 81,
place = {United States},
year = 2011,
month = 9
}
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