2003/12/24 by Petra Staubitz, Heinz Neumann, Tanja Schneider +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Antimicrobial Peptides and Activities #Biochemical and Structural Characterization #RNA and protein synthesis mechanisms
paper · pdf · doi:10.1016/s0378-1097(03)00921-2
openalex publication_date 2003/12/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
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.