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Infection and Immunity, December 2005, p. 8033-8038, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8033-8038.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

DltABCD- and MprF-Mediated Cell Envelope Modifications of Staphylococcus aureus Confer Resistance to Platelet Microbicidal Proteins and Contribute to Virulence in a Rabbit Endocarditis Model

Medical Microbiology and Hygiene Department, University of Tübingen, Tübingen, Germany,¹ Department of Medicine, Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California 90509,² LA Biomedical Research Institute, St. John's Cardiovascular Research Center, Torrance, California 90502,³ Geffen School of Medicine at UCLA, Los Angeles, California 90024⁴

Received 2 June 2005/ Returned for modification 27 June 2005/ Accepted 23 August 2005

The DltABCD and MprF proteins contribute a net positive charge to the Staphylococcus aureus surface envelope by alanylating and lysinylating teichoic acids and membrane phosphatidylglycerol, respectively. These surface charge modifications are associated with increased in vitro resistance profiles of S. aureus to a number of endogenous cationic antimicrobial peptides (CAPs), such as -defensins. The current study investigated the effects of dltA and mprF mutations on the following host factors relevant to endovascular infections: (i) in vitro susceptibility to the CAP thrombin-induced platelet microbicidal protein 1 (tPMP-1), (ii) in vitro adherence to endothelial cells (EC) and matrix proteins, and (iii) in vivo virulence in an endovascular infection model (rabbit endocarditis) in which tPMP-1 is felt to play a role in limiting S. aureus pathogenesis. Both mutations resulted in substantial increases in the in vitro susceptibility to tPMP-1 compared to that of the parental strain. The dltA (but not the mprF) mutation resulted in a significantly reduced capacity to bind to EC in vitro, while neither mutation adversely impacted in vitro binding to fibronectin, fibrinogen, or platelets. In vivo, both mutations significantly attenuated virulence in terms of early colonization of sterile vegetations and subsequent proliferation at this site (versus the parental strain). However, only the dltA mutation significantly reduced metastatic infections in kidneys and spleens compared to those in animals infected with the parental strain. These data underscore the importance of resistance to distinct CAPs and of teichoic acid-dependent EC interactions in the context of endovascular infection pathogenesis.

Editor: F. C. Fang

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