title: Molecular determinants of bacterial sensitivity and resistance to mammalian Group IIA phospholipase A2.
abstract: Group IIA secretory phospholipase A2 (sPLA(2)-IIA) of mammalian species is unique among the many structurally and functionally related mammalian sPLA(2) in their high net positive charge and potent (nM) antibacterial activity. Toward the Gram-positive bacteria tested thus far, the global cationic properties of sPLA(2)-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 sPLA(2)-IIA sensitivity despite similar intrinsic enzymatic activity of sPLA(2)-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 sPLA(2)-IIA by up to 100-fold apparently by affecting translocation of bound sPLA(2)-IIA to the cell membrane. Action of the sPLA(2)-IIA and other related sPLA(2) 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 sPLA(2)-IIA action. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.
authors.affiliation: The Inflammation Program, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA; Veterans Administration Medical Center, Iowa City, IA 52246, USA. Electronic address: jerrold-weiss@uiowa.edu.
authors.forename: Jerrold P
authors.initials: JP
authors.lastname: Weiss
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000201:enzymology* / Q000382:microbiology / Q000517:prevention & control; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D016908:Gram-Positive Bacterial Infections / Q000201:enzymology* / Q000382:microbiology / Q000517:prevention & control; D054501:Group II Phospholipases A2 / Q000378:metabolism* / Q000627:therapeutic use; D054884:Host-Pathogen Interactions; D006801:Humans; D008066:Lipolysis; D050296:Microbial Viability; D010743:Phospholipids / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D010743:Phospholipids; D054501:Group II Phospholipases A2
keywords: Bacterial sensitivity; Mammalian Group IIA; Molecular determinants; Phospholipase A2; Resistance to