title: Staphylococcus aureus subverts cutaneous defense by D-alanylation of teichoic acids.
abstract: 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.
authors.forename: Maren
authors.initials: M
authors.lastname: Simanski
authors.forename: Regine
authors.initials: R
authors.lastname: Gläser
authors.forename: Bente
authors.initials: B
authors.lastname: Köten
authors.forename: Ulf
authors.initials: U
authors.lastname: Meyer-Hoffert
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wanner
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidenmaier
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Harder
mesh_terms: D000409:Alanine / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D005798:Genes, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D012260:Ribonucleases / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D013207:Staphylococcal Skin Infections / Q000209:etiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000737:chemistry / Q000378:metabolism*; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D013682:Teichoic Acids; D023083:beta-Defensins; D012260:Ribonucleases; C470000:Ribonuclease 7; D000409:Alanine