N-Acetylglucosaminylation of Serine-Aspartate Repeat Proteins Promotes Staphylococcus aureus Bloodstream Infection |
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| Authors: | Lena Thomer Samuel Becker Carla Emolo Austin Quach Hwan Keun Kim Sabine Rauch Mark Anderson James F. LeBlanc Olaf Schneewind Kym F. Faull Dominique Missiakas |
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| Affiliation: | From the ‡Department of Microbiology, The University of Chicago, Chicago, Illinois 60637 and ;the §Pasarow Mass Spectrometry Laboratory, Semel Institute of Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences and ;the ¶Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90024 |
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| 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. |
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| Keywords: | Coagulation Factors Fibrin Glycosyltransferases Infectious Diseases Staphylococcus aureus ClfA Agglutination Serine-Aspartate Repeat |
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