title: pH Dependence of microbe sterilization by cationic antimicrobial peptides.
abstract: We recently described a family of cationic antimicrobial peptides (CAMPs) selected from a combinatorial library that exhibited potent, broad-spectrum activity at neutral pH and low ionic strength. To further delimit the utility and activity profiles of these peptides, we investigated the effects of solution conditions, such as pH and ionic strength, on the efficacy of the peptide antimicrobials against a panel of microorganisms. Peptide minimum sterilizing concentrations (MSCs) varied linearly with pH for each subtype within our family of CAMPs for all organisms tested. The peptides were much less effective against Gram-negative bacteria at high pH, consistent with a decrease in net positive charge on the peptides. A similar trend was observed for the fungus Candida albicans. Surprisingly, the opposite pH trend was observed with the Gram-positive Staphylococcus aureus. In addition, an additive ionic strength effect was observed with increasing buffer strengths at identical pH values. The extreme difference in the observed pH behavior between Gram-negative and Gram-positive organisms is attributed to the presence of native charged molecules in the much thicker peptidoglycan layer of the Gram-positive organism. The novel species-specific effects of pH observed here have important implications for applications using CAMPs and for the design of novel CAMPs.
authors: Loyola University New Orleans, Department of Chemistry, New Orleans, Louisiana, USA. walken@loyno.edu
authors: William F
authors: WF
authors: Walkenhorst
authors: J Wolfgang
authors: JW
authors: Klein
authors: Phuong
authors: P
authors: Vo
authors: William C
authors: WC
authors: Wimley
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D009994:Osmolar Concentration; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology
chemical_list: D023181:Antimicrobial Cationic Peptides
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