Open AccessMprF‐mediated biosynthesis of lysylphosphatidylglycerol, an important determinant in staphylococcal defensin resistance
Author(s) -
Staubitz Petra,
Neumann Heinz,
Schneider Tanja,
Wiedemann Imke,
Peschel Andreas
Publication year - 2004
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1016/s0378-1097(03)00921-2
Subject(s) - biosynthesis , defensin , resistance (ecology) , microbiology and biotechnology , biology , chemistry , genetics , gene , ecology , antimicrobial
Frequently bacteria are exposed to membrane‐damaging cationic antimicrobial molecules (CAMs) produced by the host's immune system (defensins, cathelicidins) or by competing microorganisms (bacteriocins). Staphylococcus aureus achieves CAM resistance by modifying anionic phosphatidylglycerol with positively charged l ‐lysine, resulting in repulsion of the peptides. Inactivation of the novel S. aureus gene, mprF , which is found in many bacterial pathogens, has resulted in the loss of lysylphosphatidylglycerol (L‐PG), increased inactivation by CAM‐containing neutrophils, and attenuated virulence. We demonstrate here that expression of mprF is sufficient to confer L‐PG production in Escherichia coli , which indicates that MprF represents the L‐PG synthase. L‐PG biosynthesis was studied in vitro and found to be dependent on phosphatidylglycerol and lysyl‐tRNA, two putative substrate molecules. Further addition of cadaverin, a competitive inhibitor of the lysyl‐tRNA synthetases, or of RNase A abolished L‐PG biosynthesis, thereby confirming the involvement of lysyl‐tRNA. This study forms the basis for further detailed analyses of L‐PG biosynthesis and its role in bacterial infections.