title: Molecular mechanisms of membrane targeting antibiotics.
abstract: The bacterial membrane provides a target for antimicrobial peptides. There are two groups of bacteria that have characteristically different surface membranes. One is the Gram-negative bacteria that have an outer membrane rich in lipopolysaccharide. Several antimicrobials have been found to inhibit the synthesis of this lipid, and it is expected that more will be developed. In addition, antimicrobial peptides can bind to the outer membrane of Gram-negative bacteria and block passage of solutes between the periplasm and the cell exterior, resulting in bacterial toxicity. In Gram-positive bacteria, the major bacterial lipid component, phosphatidylglycerol can be chemically modified by bacterial enzymes to convert the lipid from anionic to cationic or zwitterionic form. This process leads to increased levels of resistance of the bacteria against polycationic antimicrobial agents. Inhibitors of this enzyme would provide protection against the development of bacterial resistance. There are antimicrobial agents that directly target a component of bacterial cytoplasmic membranes that can act on both Gram-negative as well as Gram-positive bacteria. Many of these are cyclic peptides with a rigid binding site capable of binding a lipid component. This binding targets antimicrobial agents to bacteria, rather than being toxic to host cells. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada. Electronic address: epand@mcmaster.ca.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Walker
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Epand
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Magarvey
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008050:Lipid A / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D013045:Species Specificity
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002308:Cardiolipins; D008050:Lipid A; D008070:Lipopolysaccharides; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine
keywords: Cardiolipin; Lipid A; Lipopolysaccharide; Phosphatidylethanolamine