Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins.

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Hazenbos WL,Kajihara KK,Vandlen R,Morisaki JH,Lehar SM,Kwakkenbos MJ,Beaumont T,Bakker AQ,Phung Q,Swem LR,Ramakrishnan S,Kim J,Xu M,Shah IM,Diep BA,Sai T,Sebrell A,Khalfin Y,Oh A,Koth C,Lin SJ,Lee BC,Strandh M

doi

10.1371/journal.ppat.1003653

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003653

issue

10

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-12-02552

journal_volume

9

pub_type

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