Drug tolerance in bacteria

Abstract:

Drug tolerance is the capacity of genetically susceptible bacteria to survive the killing by bactericidal antibiotics. At population level, drug tolerance can result in slow killing kinetics or failure of sterilization by antibiotic treatment. Drug tolerance can stem from phenotypic heterogeneity or from environmentally induced stress response at population level. While various genes and pathways were shown to be implicated in bacterial drug tolerance, it is becoming clear that the common mechanism underlies the survival of antibiotic-tolerant cells is the alteration of cellular growth or metabolic state achieved by either regulation or genetic mutation, which counteracts or diminishes the killing effect induced by the drug-target interaction. Increasing clinic evidence shows that drug tolerance is a causative reason account for the requirement of lengthy treatment and the high relapse rate observed in persistent infections. Importantly, recent studies demonstrated that drug tolerance could accelerate the emergency of drug-resistant mutants. Therefore, deciphering the molecular mechanisms of antibiotic tolerance may shed light on our understanding of antibiotic killing and the adaptive evolution of antibiotic resistance, and could facilitate the development of new intervention agents and therapeutic strategies.