title: The bactericidal effect of human secreted group IID phospholipase A2 results from both hydrolytic and non-hydrolytic activities.
abstract: The Human Secreted Group IID Phospholipase A(2) (hsPLA2GIID) may be involved in the human acute immune response. Here we have demonstrated that the hsPLA2GIID presents bactericidal and Ca(2+)-independent liposome membrane-damaging activities and we have compared these effects with the catalytic activity of active-site mutants of the protein. All mutants showed reduced hydrolytic activity against DOPC:DOPG liposome membranes, however bactericidal effects against Escherichia coli and Micrococcus luteus were less affected, with the D49K mutant retaining 30% killing of the Gram-negative bacteria at a concentration of 10μg/mL despite the absence of catalytic activity. The H48Q mutant maintained Ca(2+)-independent membrane-damaging activity whereas the G30S and D49K mutants were approximately 50% of the wild-type protein, demonstrating that phospholipid bilayer permeabilization by the hsPLA2GIID is independent of catalytic activity. We suggest that this Ca(2+)-independent damaging activity may play a role in the bactericidal function of the protein.
authors.affiliation: Department of Biochemistry and Immunology, FMRP-USP, Universidade de São Paulo, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fonseca-Maldonado
authors.forename: Tatiana Lopes
authors.initials: TL
authors.lastname: Ferreira
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Ward
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D054501:Group II Phospholipases A2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008051:Lipid Bilayers; D008081:Liposomes; D016982:Micrococcus luteus / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000037:antagonists & inhibitors; D010715:Phosphatidylglycerols / Q000037:antagonists & inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; D054501:Group II Phospholipases A2; C017251:1,2-oleoylphosphatidylcholine; D002118:Calcium