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Infect. Immun. doi:10.1128/IAI.01705-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Wall teichoic acid deficiency in Staphylococcus aureus confers selective resistance to mammalian group IIA phospholipase A₂ and human defensin -3

Inflammation Program, Depts. of Microbiology, Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa and Veterans' Administration Medical Center Iowa City IA 52242; Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02134, Cellular and Molecular Microbiology, Department of Medical Microbiology and Hygiene, University Hospitals Tübingen, 72076, Tübingen, Germany

^* To whom correspondence should be addressed. Email: tomaz-koprivnjak{at}uiowa.edu.

	Abstract

Wall teichoic acids (WTA) and membrane lipoteichoic acids (LTA) are the major polyanionic polymers in the envelope of S. aureus. WTA in S. aureus plays an important role in bacteriophage attachment and bacterial adherence to certain host cells, suggesting that WTA is exposed on the cell surface and could also provide necessary binding sites for cationic antimicrobial peptides and proteins (CAMPs). Highly cationic mammalian group IIA phospholipase A₂ (gIIA PLA₂) kills S. aureus at nM concentrations by action that depends on initial electrostatic interactions, cell wall penetration, membrane phospholipid (PL) degradation and activation of autolysins. A tagO mutant of S. aureus that lacks WTA is up to 100-fold more resistant to PL degradation and killing by gIIA PLA₂ and CAMP human -defensin-3 (HBD-3) but has wild-type (wt) sensitivity to other CAMPs such as Magainin II amide, hNP1-3, LL-37 and lactoferrin. In contrast, there is little or no difference in either gIIA PLA₂ activity toward cell wall-depleted protoplasts of wt and S. aureus tagO or in binding of gIIA PLA₂ to wt and S. aureus tagO. Scanning and transmission electron microscopy reveal increased surface protrusions in S. aureus tagO that might account for reduced activity of bound gIIA PLA₂ and HBD-3 toward the tagO mutant. In summary, the absence of WTA in S. aureus causes a selective increase in bacterial resistance to gIIA PLA₂ and HBD-3, the former apparently by reducing access and/or activity of bound antibacterial enzyme to the bacterial membrane.