Bacterial Signal Transduction Systems in Antimicrobial Resistance

The ability to detect and respond in a timely fashion to environmental threats can determine whether a bacterial pathogen lives or dies. This detection and response to both host and bacterial-derived adversities is facilitated through microbial sensory and information relays commonly referred to as signal transduction systems. Signaling systems have been implicated in conferring resistance and/or tolerance to many antibiotics, especially to classes that target the cell envelope. The importance of these detection systems is evident from the nature of mutations observed within bacterial resistance-associated signaling genes detected within clinical isolates collected following antibiotic treatment. Although these bacterial signaling systems developed long before the clinical application of antimicrobials, in some cases they have evolved an expanded sensory role that now includes antimicrobials. Of particular interest is the ability of bacterial signaling systems to confer reversible resistance phenotypes, an act that saves precious cellular energy because they respond to host assaults only when the threat is present. This coordinated responsiveness then allows the pathogen to concentrate on other energy-requiring activities, such as acquiring nutrients and expressing virulence determinants. Given the importance of signaling systems in infection and resistance, some of these systems could potentially serve as novel antimicrobial targets.