Antimicrobial properties of brevinin-2-related peptide and its analogs: Efficacy against multidrug-resistant acinetobacter baumannii

J. Michael Conlon, Eman Ahmed, Eric Condamine

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48 Citations (Scopus)


Brevinin-2 related peptide (B2RP; GIWDTIKSMG10KVFAGKILQN 20L.NH2), first isolated from skin secretions of the mink frog Lithobates septentrionalis, shows broad-spectrum antimicrobial activity but its therapeutic potential is limited by moderate hemolytic activity. The peptide adopts an α-helical conformation in a membrane-mimetic solvent but amphipathicity is low. Increasing amphipathicity together with hydrophobicity by the substitutions Lys16→Leu and Lys16→Ala increased hemolytic activity approximately fivefold without increasing antimicrobial potency. The substitution Leu18→Lys increased both cationicity and amphipathicity but produced decreases in both antimicrobial potency and hemolytic activity. In contrast, increasing cationicity of B2RP without changing amphipathicity by the substitution Asp4→Lys resulted in a fourfold increase in potency against Escherichia coli [minimal inhibitory concentration (MIC) = 6 μm) and twofold increases in potency against Staphylococcus aureus (MIC = 12.5 μm) and Candida albicans (MIC = 6 μm) without changing significantly hemolytic activity against human erythrocytes (LC50 = 95 μm). The emergence of antibiotic-resistant strains of the Gram-negative bacterium Acinetobacter baumannii constitutes a serious risk to public health. B2RP (MIC = 3-6 μm) and [Lys4]B2RP (MIC = 1.5-3 μm) potently inhibited the growth of nosocomial isolates of multidrug-resistant Acinetobacter baumannii. Although the analogs [Lys 4, Lys18]B2RP and [Lys4, Ala16, Lys18]B2RP showed reduced potency against Staphylococcus aureus, they retained activity against Acinetobacter baumannii (MIC = 3-6 μm) and had very low hemolytic activity (LC50 > 200 μm).

Original languageEnglish
Pages (from-to)488-493
Number of pages6
JournalChemical Biology and Drug Design
Issue number5
Publication statusPublished (in print/issue) - Nov 2009


  • Acinetobacter baumannii
  • Antibiotic resistance
  • Brevinin-2 related peptide
  • Frog skin


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