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J Biol Chem. 2014 Feb 7;289(6):3478-86. doi: 10.1074/jbc.M113.532655. Epub 2013 Dec 16.

N-acetylglucosaminylation of serine-aspartate repeat proteins promotes Staphylococcus aureus bloodstream infection.

Author information

1
From the Department of Microbiology, The University of Chicago, Chicago, Illinois 60637 and.

Abstract

Staphylococcus aureus secretes products that convert host fibrinogen to fibrin and promote its agglutination with fibrin fibrils, thereby shielding bacteria from immune defenses. The agglutination reaction involves ClfA (clumping factor A), a surface protein with serine-aspartate (SD) repeats that captures fibrin fibrils and fibrinogen. Pathogenic staphylococci express several different SD proteins that are modified by two glycosyltransferases, SdgA and SdgB. Here, we characterized three genes of S. aureus, aggA, aggB (sdgA), and aggC (sdgB), and show that aggA and aggC contribute to staphylococcal agglutination with fibrin fibrils in human plasma. We demonstrate that aggB (sdgA) and aggC (sdgB) are involved in GlcNAc modification of the ClfA SD repeats. However, only sdgB is essential for GlcNAc modification, and an sdgB mutant is defective in the pathogenesis of sepsis in mice. Thus, GlcNAc modification of proteins promotes S. aureus replication in the bloodstream of mammalian hosts.

KEYWORDS:

Agglutination; ClfA; Coagulation Factors; Fibrin; Glycosyltransferases; Infectious Diseases; Serine-Aspartate Repeat; Staphylococcus aureus

PMID:
24344128
PMCID:
PMC3916549
DOI:
10.1074/jbc.M113.532655
[Indexed for MEDLINE]
Free PMC Article
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