Resistance to cisplatin in an E. coli B/r NalR mutant.
The effects of various mutations in DNA-repair processes have been reported to either enhance or decrease bacterial sensitivity to cis-diamminedichloroplatinum(II) (cis-DDP). In the search for other mutations affecting bacterial sensitivity to this antitumor compound, we tested the E. coli B/r BS80 mutant, which is resistant to nalidixic acid (NalR). This mutation maps in the topoisomerase II gene (gyrA subunit) and leads to cross-resistance to cis-DDP. The mechanism underlying the resistance phenotype was only partly due to decreased DNA platination. BS80 was cross-resistant to mitomycin C and, to a lesser extent, to UV light, while it was normally sensitive to MNNG. The mechanisms involved in cis-DDP and mitomycin C resistance were independent of uvrA (excision repair) and recA (SOS repair and recombination) gene expression. In contrast, UV resistance was dependent upon recA gene expression. Both the reversion to NalS in BS80 and the transduction of NalR in the parental wild type (F26) did not modify cis-DDP toxicity; in addition, platinated plasmids equally survived in BS80 and F26 strains. Hence, it is possible that selection of the NalR phenotype induced other mutation(s) than gyrA responsible for cis-DDP, mitomycin C and UV resistance and/or that lesions with a different toxic potential were introduced by cis-DDP into the BS80 and F26 chromosomes.
Bouayadi
K
K
Laboratoire de Pharmacologie et Toxicologie Fondamentales, CNRS, Toulouse, France.
Villani
G
G
Salles
B
B
D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004278:DNA, Superhelical / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D009154:Mutation; D009268:Nalidixic Acid / Q000494:pharmacology*; D010957:Plasmids; D011836:Radiation Tolerance / Q000235:genetics; D013014:SOS Response, Genetics; D014466:Ultraviolet Rays / Q000009:adverse effects
D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D008769:Methylnitronitrosoguanidine; D009268:Nalidixic Acid; D016685:Mitomycin; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin