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Background  Modification of teichoic acids with D-alanine by the products of the  dlt  operon protects Gram-positive bacteria against major antimicrobial host defense molecules such as defensins, cathelicidins, myeloperoxidase or phospholipase. The  gra RS regulatory genes have recently been implicated in the control of D-alanylation in  Staphylococcus aureus .    Results  To determine the impact of the GraRS regulatory system on resistance to antimicrobial host defense mechanisms and virulence of  S. aureus , we compared inactivation of  S. aureus  SA113 wild type and its isogenic  gra RS deletion mutant by the human cathelicidin LL-37 or human neutrophil granulocytes  in vitro , and the ability to cause infection  in vivo . We show here that  gra RS deletion considerably alters bacterial surface charge, increases susceptibility to killing by human neutrophils or the defense peptide LL-37, and attenuates virulence of  S. aureus  in a mouse infection model.    Conclusion  Our results indicate that  S. aureus  can regulate its surface properties in order to overcome innate host defenses.

The GraRS regulatory system controls Staphylococcus aureus susceptibility to antimicrobial host defenses