Eagle Effect in Nonreplicating Persister Mycobacteria.
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.
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
Mu-Lu
ML
Wu
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
Jasmie
J
Tan
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore thomas_dick@nuhs.edu.sg.
Thomas
T
Dick
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology; D003470:Culture Media; D027081:DNA Gyrase; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology*; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000254:growth & development; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D059003:Topoisomerase Inhibitors / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D003470:Culture Media; D024841:Fluoroquinolones; D011500:Protein Synthesis Inhibitors; D059003:Topoisomerase Inhibitors; D002701:Chloramphenicol; D027081:DNA Gyrase