Eagle Effect in Nonreplicating Persister Mycobacteria.
Mu-Lu Wu, Jasmie Tan, Thomas Dick
Author Information
Mu-Lu Wu: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
Jasmie Tan: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
Thomas Dick: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore thomas_dick@nuhs.edu.sg.
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.
