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.affiliation: Department of Microbiology & Molecular Genetics, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Arunima
authors.initials: A
authors.lastname: Mishra
authors.forename: Bharanidharan
authors.initials: B
authors.lastname: Devarajan
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Reardon
authors.forename: Prabhat
authors.initials: P
authors.lastname: Dwivedi
authors.forename: Vengadesan
authors.initials: V
authors.lastname: Krishnan
authors.forename: John O
authors.initials: JO
authors.lastname: Cisar
authors.forename: Asis
authors.initials: A
authors.lastname: Das
authors.forename: Sthanam V L
authors.initials: SV
authors.lastname: Narayana
authors.forename: Hung
authors.initials: H
authors.lastname: Ton-That
mesh_terms: D000190:Actinomyces / Q000378:metabolism*; D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001212:Asialoglycoproteins / Q000378:metabolism; D001422:Bacterial Adhesion; D018441:Biofilms; D018360:Crystallography, X-Ray; D060748:Fetuins / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016415:Sequence Alignment; D019533:Streptococcus oralis / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000166:cytology / Q000378:metabolism*; D014070:Tooth / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D001212:Asialoglycoproteins; D060748:Fetuins; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; C017029:asialofetuin; D036781:Fimbriae Proteins