title: Bacterial species selective toxicity of two isomeric alpha/beta-peptides: role of membrane lipids.
abstract: We have studied how membrane interactions of two synthetic cationic antimicrobial peptides with alternating alpha- and beta-amino acid residues ("alpha/beta-peptides") impact toxicity to different prokaryotes. Electron microscopic examination of thin sections of Escherichia coli and of Bacillus subtilis exposed to these two alpha/beta-peptides reveals different structural changes in the membranes of these bacteria. These two peptides also have very different effects on the morphology of liposomes composed of phosphatidylethanolamine and phosphatidylglycerol in a 2:1 molar ratio. Freeze fracture electron microscopy indicates that with this lipid mixture, alpha/beta-peptide I induces the formation of a sponge phase. 31P NMR and X-ray diffraction are consistent with this conclusion. In contrast, with alpha/beta-peptide II and this same lipid mixture, a lamellar phase is maintained, but with a drastically reduced d-spacing. alpha/beta-Peptide II is more lytic to liposomes composed of these lipids than is I. These findings are consistent with the greater toxicity of alpha/beta-peptide II, relative to alpha/beta-peptide I, to E. coli, a bacterium having a high content of phosphatidylethanolamine. In contrast, both alpha/beta-peptides display similar toxicity toward B. subtilis, in accord with the greater anionic lipid composition in its membrane. This work shows that variations in the selectivity of these peptidic antimicrobial peptides toward different strains of bacteria can be partly determined by the lipid composition of the bacterial cell membrane.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada. epand@mcmaster.ca
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Epand
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Schmitt
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
authors.forename: Arindam
authors.initials: A
authors.lastname: Sen
authors.forename: Michèle
authors.initials: M
authors.lastname: Auger
authors.forename: Donald W
authors.initials: DW
authors.lastname: Hughes
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000254:growth & development* / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000254:growth & development* / Q000648:ultrastructure; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008563:Membrane Lipids