%0 Journal Article
%T Novel Staphylococcal Glycosyltransferases SdgA and SdgB Mediate Immunogenicity and Protection of Virulence-Associated Cell Wall Proteins
%A Wouter L. W. Hazenbos equal contributor
%A Kimberly K. Kajihara equal contributor
%A Richard Vandlen
%A J. Hiroshi Morisaki
%A Sophie M. Lehar
%A Mark J. Kwakkenbos
%A Tim Beaumont
%A Arjen Q. Bakker
%A Qui Phung
%A Lee R. Swem
%A Satish Ramakrishnan
%A Janice Kim
%A Min Xu
%A Ishita M. Shah
%A Binh An Diep
%A Tao Sai
%A Andrew Sebrell
%A Yana Khalfin
%A Angela Oh
%A Chris Koth
%A S. Jack Lin
%A Byoung-Chul Lee
%A Magnus Strandh
%A Klaus Koefoed
%A Peter S. Andersen
%A Hergen Spits
%A Eric J. Brown
%A Man-Wah Tan
%A Sanjeev Mariathasan
%J PLOS Pathogens
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1003653
%X Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to host tissues by binding to extracellular matrix proteins such as fibrinogen. However, the biological siginificance of the SDR-domain and its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two bacterial species. Genetic and biochemical data demonstrated that these two glycosyltransferases directly bind and covalently link N-acetylglucosamine (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending the sugar residues proximal to the target Ser-Asp repeats, followed by additional modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an immunodominant epitope for highly opsonic human antibodies, which represent up to 1% of total human IgG. Deletion of these glycosyltransferases renders SDR-proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus, SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them against host proteolytic activity, and yet generates major eptopes for the human anti-staphylococcal antibody response, which may represent an ongoing competition between host and pathogen.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003653