Eagle Effect in Nonreplicating Persister Mycobacteria

• Published in: Antimicrobial agents and chemotherapy Vol. 59; no. 12; pp. 7786 - 7789
• Main Authors: Wu, Mu-Lu, Tan, Jasmie, Dick, Thomas
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.12.2015
• Subjects: Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Chloramphenicol - pharmacology; Culture Media; DNA Gyrase; Dose-Response Relationship, Drug; Fluoroquinolones - pharmacology; Mechanisms of Action: Physiological Effects; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections, Nontuberculous - microbiology; Mycobacterium smegmatis; Mycobacterium smegmatis - drug effects; Mycobacterium smegmatis - growth & development; Protein Synthesis Inhibitors - pharmacology; Topoisomerase Inhibitors - pharmacology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01476-15

We determined the microbicidal activities of antibacterials against nonreplicating Mycobacterium smegmatis grown in a starvation-based Loebel model for persistence. Whereas most drugs lost their activity, fluoroquinolones retained lethal potency. Dose-response characterizations showed a paradoxical more-drug-kills-less Eagle effect. Pretreatment of cultures with chloramphenicol blocked the lethal action of the gyrase inhibitors. These results suggest that fluoroquinolones at low concentrations trigger a protein synthesis-dependent cell death pathway and shut off this suicide pathway at elevated concentrations.