Eagle effect in nonreplicating persister mycobacteria

Abstract

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. Doseresponse 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.