Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis.
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.
Chatterji
M
M
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India 560012.
Unniraman
S
S
Mahadevan
S
S
Nagaraja
V
V
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000890:Anti-Infective Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology; D001427:Bacterial Toxins / Q000235:genetics / Q000494:pharmacology; D001430:Bacteriocins / Q000235:genetics / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000145:classification* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D005047:Etoposide / Q000494:pharmacology; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D059005:Topoisomerase II Inhibitors
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001430:Bacteriocins; C068356:CcdB protein, Plasmid F; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D059005:Topoisomerase II Inhibitors; C020411:microcin; D002939:Ciprofloxacin; D005047:Etoposide; D000251:Adenosine Triphosphatases; D027081:DNA Gyrase