The Bacterial Defensin Resistance Protein MprF Consists of Separable Domains for Lipid Lysinylation and Antimicrobial Peptide Repulsion

• DOI: 10.1371/journal.ppat.1000660
• Publication Date: 2009-11-12T22:39:18Z
• Authors: Christoph M. Ernst; Petra Staubitz; Nagendra N. Mishra; Soo-Jin Yang; Gabriele Hornig; Hubert Kalbacher; Arnold S. Bayer; Dirk Kraus; Andreas Peschel
• Keywords: Phosphatidylglycerol; C2 domain

Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides (CAMPs) by the multiple peptide factor (MprF) protein. MprF plays a crucial role in Staphylococcus aureus virulence and it is involved CAMP-like antibiotic daptomycin. large membrane protein that modifies anionic phospholipid phosphatidylglycerol with l-lysine, thereby diminishing affinity for CAMPs. Its widespread occurrence recommends as target novel antimicrobials, although mode of action has remained incompletely understood. We demonstrate hydrophilic C-terminal domain six fourteen proposed trans-membrane segments are sufficient full-level lysyl-phosphatidylglycerol (Lys-PG) production several conserved amino acid positions indispensable Lys-PG production. Notably, did not lead efficient CAMP most inner leaflet cytoplasmic when N-terminal hydrophobic was absent, indicating this part. The alone confer or repulsion test cytochrome c. However, coexpressed synthase either one two separate proteins, achieved. Moreover, only coexpression domains led translocation outer c repulsion, facilitates flipping Lys-PG. Thus, represents new class lipid-biosynthetic enzymes separable functional synthesize facilitate translocation. Our study unravels details on molecular basis an important immune evasion mechanism may help employ anti-virulence drugs.