Identification and characterization of amphipathic antimicrobial peptides with broad spectrum activity against multi-drug resistant bacteria.

Abstract

Antimicrobial peptides (AMPs) are potential alternatives to antibiotics given the reduced likelihood of resistance and their high selectivity towards bacteria. AMPs with activity against antibiotic-resistant bacteria have been reported. The aim of this study is to characterize the activity of novel BP100 analogues against multidrug-resistant bacteria. Eleven bacterial strains representing five pathogenic species were used to evaluate the antimicrobial activity of 26 peptides. An initial screen was performed at 50 µg/ml, and those peptides that inhibited ≈90 % of growth of all strains were selected. Minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), inhibition in biofilm formation, time kill assays, stability in human serum and in vivo toxicity were assessed. BP607, BP76 and BP145, had broad activity against multidrug-resistant bacteria. MICs ranged between 3.13 and 50 µg/ml, whereas MBCs ranged between 6.25 and 100 µg/ml. Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli were the most susceptible species. At 2x the MIC, all compounds were bactericidal after 6h. BP76 inhibited ≥ 76.77 % of K. pneumoniae and E. coli biofilm formation at subinhibitory concentrations. BP145 had improved serum stability and lower toxicity compared to BP607. In conclusion, BP145 and BP76 demonstrate broad antimicrobial activity, are active at non-toxic concentrations, feature bactericidal activity at 6h and inhibit biofilm formation.