Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis.

Abstract

Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA gyrase. Information regarding these various inhibitors comes from studies performed with the enzyme from Escherichia coli, and subsequent analyses have also primarily been confined to this system. We have carried out a detailed analysis of the effect of various groups of inhibitors on Mycobacterium smegmatis gyrase and demonstrate differential susceptibility of the E. coli and M. smegmatis gyrases. Interestingly, M. smegmatis gyrase was refractory to the plasmid-borne proteinaceous inhibitors CcdB and microcin B17. Ciprofloxacin, a fluoroquinolone, showed a 10-fold reduction in efficacy against M. smegmatis compared with E. coli gyrase. We have also shown that etoposide, an antineoplastic drug, inhibits DNA gyrase activity by trapping the gyrase-DNA complex. DNA gyrases from both E. coli and M. smegmatis were susceptible to etoposide at comparable levels.