Clarifying the Link between Toxin–Antitoxin Modules and Bacterial Persistence

• Published in: Journal of molecular biology 2019-08, Vol.431 (18), p.3462-3471
• Main Authors: Ronneau, Séverin, Helaine, Sophie
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; antibiotics; Antitoxins - pharmacology; Bacteria - drug effects; Bacteria - metabolism; Bacterial Infections - drug therapy; Bacterial Physiological Phenomena; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - physiology; Drug Tolerance - physiology; Microbial Sensitivity Tests; Persistence; Stress, Physiological; tolerance; Toxin-antitoxin modules; Toxin-Antitoxin Systems - physiology
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2019.03.019

While most of a bacterial population is killed upon antibiotic exposure, a fraction transiently exhibits a multidrug-tolerant phenotype termed antibiotic persistence. This phenomenon enables the bacteria to escape killing by drugs and is presumed to be, at least partly, responsible for the recalcitrance of many bacterial infections. For this reason, understanding mechanisms allowing a fraction of a bacterial population to become transiently multidrug-tolerant represents an essential step to eradicate these persisting subpopulations. Toxin–antitoxin (TA) systems were proposed as perfect candidates to control this phenomenon since these elements are often mutated in high-persistence screens and overexpression of these toxins often increases persister frequency in a defined population. However, the accumulation of evidence and counter-evidence for the role of TA systems in bacterial persistence has led to general confusion in the field. In this review, we summarize evidence that link TA modules to antibiotic bacterial persistence. Then, we discuss the limitations of work on these stress-responsive modules as well as bacterial persistence in general. [Display omitted] •Antibiotic persisters are multidrug-tolerant bacteria.•Toxin–antitoxin systems were proposed as perfect candidates to control this phenomenon.•Accumulation of evidence and counter-evidence for the role of TA systems in bacterial persistence has led to general confusion in the field.•We summarize evidence that link TA modules to antibiotic bacterial persistence.