mprF

MprF, short for multiple peptide resistance factor, is a bifunctional membrane protein found in many Gram-positive bacteria. It is encoded by the mprF gene and plays a key role in resistance to cationic antimicrobial peptides (CAMPs) and certain antibiotics by modifying the bacterial cell envelope.

The enzyme has two overlapping activities. The N-terminal region functions as a lysyl-phosphatidylglycerol (Lys-PG) synthase, using lysyl-tRNA as the amino donor to attach L-lysine to phosphatidylglycerol, forming Lys-PG. The C-terminal region acts as a flippase that translocates Lys-PG from the inner to the outer leaflet of the cytoplasmic membrane. The accumulation of Lys-PG on the outer surface reduces the net negative charge of the cell surface, weakening electrostatic interactions with positively charged antimicrobial peptides and certain antibiotics such as daptomycin.

MprF homologs are widespread among several pathogenic bacteria, including Staphylococcus aureus, Enterococcus faecalis, and Listeria monocytogenes. Variation in mprF can influence the degree of CAMP resistance and can impact virulence and antibiotic susceptibility.

Clinical and therapeutic relevance is focused on the role of MprF in modulating bacterial defenses. Because inhibition or low expression of MprF can increase bacterial susceptibility to CAMPs and to certain antibiotics, MprF is considered a potential target for antimicrobial adjuvants aimed at restoring or enhancing the efficacy of host defenses and cationic antimicrobial therapies.