FLUOROQUINOLONE ACTION IN MYCOBACTERIA - SIMILARITY WITH EFFECTS IN ESCHERICHIA-COLI AND DETECTION BY CELL LYSATE VISCOSITY

Fluoroquinolones are potent antibacterial agents that are being used a s therapeutic agents for the treatment of multidrug-resistant tubercul osis, To better understand fluoroquinolone action in mycobacteria, the effects of ciprofloxacin were examined, DNA synthesis was inhibited r apidly in Mycobacterium smegmatis, DNA cleavage was readily observed b y an empirical assay of cell lysate viscosity, and cell growth was blo cked, These data are explained by the formation of gyrase-DNA-ciproflo xacin complexes that block replication fork movement, The bactericidal action of ciprofloxacin against M. smegmatis, Mycobacterium bollis BC G, and Escherichia coli occurred more slowly in cells with longer doub ling times, The bactericidal effect against M. bovis BCC was partially blocked by pretreatment with chloramphenicol, an inhibitor of protein synthesis, and by very high concentrations of ciprofloxacin itself, S imilar responses occur when E. coli is treated with ciprofloxacin. The se similarities between E. coli and mycobacteria indicate that results from extensive fluoroquinolone studies with E. coli can be applied to mycobacteria, A simple viscometric assay of DNA cleavage is described , The assay is expected to he useful for screening new fluoroquinolone derivatives for increased effectiveness against clinically important bacteria.