Membrane-Bound Conformations of Antimicrobial Agents and Their Modes of Action

Abstract

Abstract All antimicrobial agents are inherently membrane active and the complex interactions involved can lead to considerable conformational changes in the agents, while also inducing structural rearrangements of membrane lipids. Such structural modifications can trigger series of events enabling the agent to affect the structural integrity of the microbial membrane or translocate to the interior of the microbial cell. Therapeutic use of such agents requires a detailed understanding of the interaction of such antimicrobial agents with bacterial membranes. It is of interest to note that despite the existence of diversity in chemical compositions of many naturally occurring antimicrobial agents, the possible number of secondary structure conformations that they possess, either in solution or in membrane environment, is very small in number. In spite of considerable effort put in to probe the relationship between secondary structure and mode of antimicrobial action over the past two decades through experiments and simulations, a detailed understanding of the same is yet to be achieved. Furthermore, recent experimental and simulation results suggest that built-in well-defined secondary conformations such as α-helix or β-sheet may not be the essential feature of potent antimicrobial agents, but rather the ability of these agents to acquire amphiphilic conformations, involving the spatial separation of charged and hydrophobic moieties, near the bacterial membrane. In this chapter, we review different antimicrobial agents that have been the focus of various studies with special emphasis on computer simulations and their role in understanding the interactions of biomimetic antimicrobial polymers, based on methacrylate copolymers, with bacterial membranes.