Target-Mediated Antibacterial Resistance

Abstract

Bacteria have evolved a variety of methods to avoid the lethal action of antimicrobial agents. Among the more common and diverse mechanisms of resistance are alterations of the antimicrobial targets. It is axiomatic that all antimicrobial agents have targets—proteins or other structures within the bacterial cell that are essential to the structure, growth, and/or function of the microorganism. In order to do their job effectively, antimicrobial agents must interact with these targets in a manner that precludes the normal functioning of the target molecule. Moreover, their interactions with the target must be fairly specific, otherwise the potential for interaction with human molecules, and thereby the potential for toxicity, will be increased. In a circumstance in which the antibiotic–target interaction is specific, changes in the target structure or in the environment immediately surrounding the target can have a profound impact on target–antibiotic interaction. This interaction can result in resistance, as long as the changes do not in a meaningful way impact the ability of the target molecule to serve its function in cellular structure or metabolism. The frequent incorporation of the genetic underpinnings of these modifications into mobile elements has facilitated the wide dissemination of resistance.