Ciprofloxacin and etoposide (VP16) produce a similar pattern of DNA cleavage in a plasmid of an archaebacterium.
The fluoroquinolone ciprofloxacin, an inhibitor of eubacterial DNA gyrase, induces single- and double-stranded DNA breaks in the plasmid pGRB-1 from the halophilic archaebacterium Halobacterium GRB when the cells are treated by this drug in a magnesium-depleted medium. This reaction is prevented by a dose of novobiocin known to specifically inhibit DNA gyrase. Cleavage of pGRB-1 DNA induced by either ciprofloxacin or the antitumoral drug etoposide (VP16) produces DNA fragments of identical lengths. These results indicate that ciprofloxacin, novobiocin, and etoposide have a common target in Halobacterium GRB: an archaebacterial type II DNA topoisomerase. The similarity of DNA cleavage patterns induced by ciprofloxacin and etoposide is a new and strong argument that quinolone and epipodophyllotoxins have the same mode of interaction with the DNA-DNA topoisomerase II complexes. The plasmid pGRB-1 could be used to prescreen in the same system both antibiotics that inhibit bacterial gyrase and antitumoral drugs that inhibit eukaryotic DNA topoisomerase II.
Sioud
M
M
Institut de Microbiologie, Université Paris-Sud, Centre d'Orsay, France.
Forterre
P
P
D002939:Ciprofloxacin / Q000494:pharmacology*; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology*; D006217:Halobacterium / Q000187:drug effects / Q000235:genetics*; D009675:Novobiocin / Q000494:pharmacology; D010957:Plasmids / Q000187:drug effects*
D009675:Novobiocin; D002939:Ciprofloxacin; D005047:Etoposide