MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads to protection against oxygen-independent neutrophil killing.
Staphylococcus aureus achieves resistance to defensins and similar cationic antimicrobial peptides (CAMPs) by modifying anionic membrane lipids via MprF with L-lysine, which leads to repulsion of these host defense molecules. S. aureus DeltamprF, which lacks the modification, was very efficiently killed by neutrophil defensins and CAMP-producing leukocytes, even when oxygen-dependent killing was disrupted, but was as susceptible as wild-type bacteria to inactivation by myeloperoxidase or human monocytes lacking defensins. These results demonstrate the impact and specificity of MprF-mediated CAMP resistance and underscore the role of defensin-like peptides in innate host defense.
Kristian
Sascha A
SA
Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany.
Dürr
Manuela
M
Van Strijp
Jos A G
JA
Neumeister
Birgid
B
Peschel
Andreas
A
D019881:Aminoacyltransferases; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D023082:Defensins / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology*; D010100:Oxygen / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D023082:Defensins; D010715:Phosphatidylglycerols; D010743:Phospholipids; D019881:Aminoacyltransferases; C429146:mprF protein, Staphylococcus aureus; D008239:Lysine; D010100:Oxygen