title: Low pH Enhances the Action of Maximin H5 against Staphylococcus aureus and Helps Mediate Lysylated Phosphatidylglycerol-Induced Resistance.
abstract: Maximin H5 (MH5) is an amphibian antimicrobial peptide specifically targeting Staphylococcus aureus. At pH 6, the peptide showed an improved ability to penetrate (ΔΠ = 6.2 mN m(-1)) and lyse (lysis = 48%) Staphylococcus aureus membrane mimics, which incorporated physiological levels of lysylated phosphatidylglycerol (Lys-PG, 60%), compared to that at pH 7 (ΔΠ = 5.6 mN m(-1) and lysis = 40% at pH 7) where levels of Lys-PG are lower (40%). The peptide therefore appears to have optimal function at pH levels known to be optimal for the organism's growth. MH5 killed S. aureus (minimum inhibitory concentration of 90 μM) via membranolytic mechanisms that involved the stabilization of α-helical structure (approximately 45-50%) and showed similarities to the "Carpet" mechanism based on its ability to increase the rigidity (Cs(-1) = 109.94 mN m(-1)) and thermodynamic stability (ΔGmix = -3.0) of physiologically relevant S. aureus membrane mimics at pH 6. On the basis of theoretical analysis, this mechanism might involve the use of a tilted peptide structure, and efficacy was noted to vary inversely with the Lys-PG content of S. aureus membrane mimics for each pH studied (R(2) ∼ 0.97), which led to the suggestion that under biologically relevant conditions, low pH helps mediate Lys-PG-induced resistance in S. aureus to MH5 antibacterial action. The peptide showed a lack of hemolytic activity (<2% hemolysis) and merits further investigation as a potential template for development as an antistaphylococcal agent in medically and biotechnically relevant areas.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire , Preston PR1 2HE, U.K.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.affiliation: School of Forensic and Investigative Science, University of Central Lancashire , Preston PR1 2HE, U.K.
authors.forename: Leslie Hg
authors.initials: LH
authors.lastname: Morton
authors.affiliation: School of Forensic and Investigative Science, University of Central Lancashire , Preston PR1 2HE, U.K.
authors.forename: Frederick
authors.initials: F
authors.lastname: Harris
authors.affiliation: School of Applied Science, London South Bank University , 103 Borough Road, London SE1 0AA, U.K.
authors.forename: David A
authors.initials: DA
authors.lastname: Phoenix
mesh_terms: D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D012756:Sheep; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010715:Phosphatidylglycerols; C002285:lysylphosphatidylglycerol; D008239:Lysine