Staphylococcus aureus subverts cutaneous defense by d-alanylation of teichoic acids

The Gram‐positive bacterium Staphylococcus aureus is a frequent skin colonizer that often causes severe skin infections. It has been reported that neutralizing the negatively charged bacterial surface through the incorporation of d‐alanine in its teichoic acids confers reduced susceptibility of S. aureus towards cationic antimicrobial peptides (AMPs). Using a S. aureus strain deficient in d‐alanylated teichoic acids (dltA mutant), we demonstrate that d‐alanylation of its surface reduces the susceptibility of S. aureus to skin‐derived AMPs such as RNase 7 and human beta‐defensins. This is accompanied by a higher killing activity of skin extracts towards the S. aureus dltA mutant as well as towards clinical isolates expressing lower levels of dltA. We conclude that modulation of cell envelope d‐alanylation may help S. aureus to persist on human skin through evasion of cutaneous innate defense provided by cationic skin‐derived AMPs.