Background 
Staphylococcus aureus, a frequent cause of human infections, is highly resistant to antimicrobial factors of the innate immune system such as cationic antimicrobial peptides (CAMPs) [1,2] which are produced by epithelial cells and neutrophils [3,4].
These peptides generally contain 10-50 amino acids and have positive net charges [5].
Due to their cationic properties, CAMPs can easily bind to the highly negatively charged bacterial cell envelope and inactivate bacteria, e.g. by forming pores in the bacterial membrane leading to bacterial lysis [6].
S. aureus has evolved mechanisms to alter the anionic charge of cell surface components to gain resistance to a broad variety of cationic antimicrobial factors such as CAMPs [7], phospholipase A2 [8], myeloperoxidase [9], or lysozyme [10].
One such mechanism is based upon modification of phospholipids in the cytoplasmic membrane by introducing a positively charged lysyl group into anionic phosphatidylglycerol by the MprF protein, thereby neutralizing the net charge of the membrane surface [11,12].
A similar reaction is mediated by products of the dltABCD operon, which are responsible for attachment of positively charged D-alanine residues into negatively charged phosphate groups in the backbone of teichoic acids [7,9].
Mechanisms involved in the regulation of these resistance factors are not yet well understood in Gram-positive bacteria.
Herbert et al. recently found that the S. aureus two-component regulatory system graRS positively regulates expression of the dlt operon.
In a S. aureus SA113 graRS deletion mutant, the content of D-alanine in teichoic acids was reduced by 47% and the mutant showed reduced resistance to various antibiotics including polymyxin B, gallidermin, and vancomycin [10,13].
Accordingly, graRS have previously been implicated in regulation of vancomycin intermediary resistance [14].
As the dlt operon plays a key role in S. aureus resistance to cationic antimicrobial host molecules, the graRS system may be important in evasion of host defense mechanisms such as cationic antimicrobial peptides and neutrophil killing.
