lysylphosphatidylglycerol

Lysylphosphatidylglycerol (LPG) is a positively charged glycerophospholipid produced by certain bacteria through the modification of phosphatidylglycerol (PG) with the amino acid lysine. The addition of the lysine headgroup reduces the overall negative surface charge of the bacterial membrane, influencing interactions with cationic antimicrobial peptides and some antibiotics.

Biosynthesis and mechanism: LPG formation is catalyzed by the bifunctional enzyme MprF, often described as a lysyl-phosphatidylglycerol synthase with an associated flippase activity. In the first step, MprF transfers L-lysine from lysyl-tRNA to PG to form LPG. In many species, a membrane domain then flips LPG from the inner to the outer leaflet of the cytoplasmic membrane, increasing LPG exposure on the cell surface.

Distribution and function: LPG has been detected in multiple Gram-positive genera, notably Staphylococcus aureus, Enterococcus faecalis, and various Streptococcus species. By lowering surface charge, LPG reduces binding of cationic antimicrobial peptides produced by the host immune system and can confer resistance to certain antibiotics, including daptomycin and polymyxins in some contexts. Production of LPG can contribute to virulence traits such as enhanced survival in hostile environments and, in some cases, altered biofilm formation; effects are species- and context-dependent.

Clinical relevance: Because LPG synthesis helps bacteria withstand host defenses and antibiotic pressure, MprF and LPG are considered potential targets for adjuvant therapies aimed at restoring susceptibility to cationic antimicrobial peptides. Detection and study typically involve lipidomics methods (e.g., mass spectrometry) or analyses of mprF homologs in bacterial genomes.