Membrane interaction of polymyxin B and synthetic analogues studied in biomimetic systems: implications for antibacterial action

Abstract

Membrane-active antimicrobial peptides, such as polymyxin B (PxB), are currently in the spotlight as potential candidates to overcome bacterial resistance. We have designed synthetic analogs of PxB in order to determine the structural requirements for membrane action. Since the mechanism of action of PxB involves interaction with both the outer membrane and the cytoplasmic membrane of Gram negative bacteria, we have used an approach based on mimicking the outer layers of these membranes using monolayers, Langmuir-Blodgett films and unilamelar vesicles, and applying a battery of biophysical methods in order to dissect the different events of membrane interaction. Collectively, results indicate that the PxB analogues act in the bacterial membrane by the same mechanism than PxB, and that cationic amphipathicity determines peptide activity.