Attività in vitro di nuovi antibiotici peptidici

Abstract

Antimicrobial-peptide-based therapies could represent a reliable alternative to overcome antibiotic resistance, since they offer some potential advantages such as the rapid microbicidial activity and multiple activity against a broad spectrum of bacterial pathogens. Three synthetic antimicrobial peptides (AMPs) designed by using proprietary screening software develop in house were synthesized and tested against nine reference strains. The AMPs showed structural similarity to cyclic beta-sheet defence peptides. The antimicrobial activity was dose-dependent with a Minimum Inhibitory Concentration (MIC) of 0.4-25μg/ml for Gram negative e 1.72-100μg/ml for Gram positive. No significant haemolytic activity was observed at 100μg/ml for all tested peptides. Interestigly, at high salt environment, the antibacterial activity was generally maintained for Gram-negative bacteria. The three tested peptides (AMP2041, AMP72, AMP126) achieve complete bacterial killing in 20 min or less against Gram-negative bacteria, AMP2041 and AMP72 showed at 12.5μg/ml, a linear time-dependent membrane permeabilization with an equilibrium rate of 22 min and 19 min, respectively, while AMP126 failed to reach equilibrium within the observation period (120 min). In combination with conventional anti-infective agents (levofloxacin or aminoglycosides) AMP126 e AMP2041 showed additive activity in comparison with colistin. In conclusion, our results suggest (i) high activity against Gram-negative, (ii) low if any haemolytic activity at 50-100xMIC, (iii) the MIC value of the combination AMPs-conventional antibiotics was lower than MIC of single agents alone, encouraging to conduct further studies on animal models.