Influence of DNA supercoiling on cisplatin toxicity in Escherichia coli K-12

DNA supercoiling is known to modulate the activity of numerous promoters in vitro and in vivo. Moreover, it has been reported to modulate the rate of formation of cisplatin/DNA crosslinks in vitro. In order to address the question of how the topology influences CDDP toxicity in E. coli, three mutants with altered gyrase activity which led to a decrease of about 25% in superhelical density were studied. Mutant strains gyrA₂₂₄ and gyrB₂₂₅ showed similar sensitivity to CDDP as the parental strain while the gyrB₂₂₆ mutant was resistant. This resistance was abolished in uvrA (excision-repair) and recA (recombination and SOS processes) mutant derivatives. Thus supercoiling might play a role as an indirect modulator of CDDP toxicity in bacteria by interfering with repair processes.