Targeting Antibiotic Tolerance, Pathogen by Pathogen

Abstract

Antibiotic tolerance, the capacity of genetically susceptible bacteria to survive the lethal effects of antibiotic treatment, plays a critical and underappreciated role in the disease burden of bacterial infections. Here, we take a pathogen-by-pathogen approach to illustrate the clinical significance of antibiotic tolerance and discuss how the physiology of specific pathogens in their infection environments impacts the mechanistic underpinnings of tolerance. We describe how these insights are leading to the development of species-specific therapeutic strategies for targeting antibiotic tolerance and highlight experimental platforms that are enabling us to better understand the complexities of drug-tolerant pathogens in in vivo settings. Lack of efficacy of antibiotic treatment presents a critical challenge to clinical management of bacterial infections. This review discusses the significance of antibiotic tolerance as the culprit of this challenge and its underlying mechanism as the target for future therapeutic development.