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Antibacterial Properties of Dermaseptin S4 Derivatives under Extreme Incubation Conditions

Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, 32000 Haifa, Israel

Received 16 June 2005/ Returned for modification 22 July 2005/ Accepted 14 November 2005

Antibacterial properties of the frog-derived peptide dermaseptin S4 and a series of synthetic derivatives against the food pathogen Escherichia coli O157:H7 were investigated under extreme incubation conditions. The 28-mer analog K₄K₂₀S4 (P₂₈) displayed an MIC of 8 µM and rapid bactericidal kinetics under standard culture conditions. Potent bactericidal properties were maintained at high salt concentrations, under acidic or basic conditions, and at extreme temperatures. The N-terminal 14-mer sequence (P₁₄) displayed higher potency (MIC, 4 µM) but only within a narrow range of incubation conditions, pointing to the importance of the C-terminal domain of P₂₈. The potency range was reextended upon conjugation of aminododecanoic acid to P₁₄. The resulting lipopeptide was even more potent (MIC, 2 µM) and affected bacterial viability under most of the conditions tested, including in commercial apple juice. The mechanistic implications of peptides' hydrophobicity, charge, structure, and binding to an idealized membrane were probed and are discussed here. Collectively, the data indicate interest in simple peptide-based compounds for design of antimicrobials that affect pathogens under a variable range of incubation conditions.