Molecular determinants of bacterial sensitivity and resistance to mammalian Group IIA phospholipase A2

Abstract

Group IIA secretory phospholipase A2 (sPLA2-IIA) of mammalian species is unique among the many structurally and functionally related mammalian sPLA2 in their high net positive charge and potent (nM) antibacterial activity. Toward the Gram-positive bacteria tested thus far, the global cationic properties of sPLA2-IIA are necessary for optimal binding to intact bacteria and penetration of the multi-layered thick cell wall, but not for the degradation of membrane phospholipids that is essential for bacterial killing. Various Gram-positive bacterial species can differ as much as 1000-fold in sPLA2-IIA sensitivity despite similar intrinsic enzymatic activity of sPLA2-IIA toward the membrane phospholipids of various bacteria. d-alanylation of wall- and lipo-teichoic acids in Staphylococcus aureus and sortase function in Streptococcus pyogenes increase bacterial resistance to sPLA2-IIA by up to 100-fold apparently by affecting translocation of bound sPLA2-IIA to the cell membrane. Action of the sPLA2-IIA and other related sPLA2 against Gram-negative bacteria is more dependent on cationic properties of the enzyme near the amino-terminus of the protein and collaboration with other host defense proteins that produce alterations of the unique Gram-negative bacterial outer membrane that normally represents a barrier to sPLA2-IIA action. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.