Dioxidine induces bacterial resistance to antibiotics

Abstract

The capability of the dioxidine drug to cause bacterial resistance to antibiotics was studied. The study was performed with the use of a bioluminescent test and the recombinant E. coli strains MG 1655 (pSoxS-lux), MG1655 (pKatG-lux), MG1655 (pRecA-lux), and MG1655 (pColD-lux). The strains harbored plasmids with the operon luxCDABE from the photobacteria Photorhabdus luminescens under control of the corresponding E. coli stress-inducible promoters. The mutation frequency of the stable mutants was found by conventional methods for nonpathogenic and opportunistic strains of E. coli, Bacillus amyloliquefaciens, and Klebsiella pneumoniae. Dioxidine was shown to induce the promoters PrecA and Pcda in E. coli MG1655, which suggests the induction of the SOS-response in bacterial cells. The Pcda induction was higher than with PrecA. The value of the induction coefficient was highest if the dioxidine concentration was 2.25 × 10^–5 M. Moreover, this drug enhanced the induction of the SoxS and KatG promoters responding to the superoxide anion radical and hydrogen peroxide, which suggests possible participation of oxidative mechanisms in dioxidine DNA damage. The maximal value of the induction coefficient was also observed under conditions of 2.25 × 10^–5 M. Dioxidine can induce mutations leading to antibiotic resistance in all bacterial strains studied. An increase in mutation frequency was observed for rifampicin (twofold), ciprofloxacin (sixfold), and azithromycin (fourfold). These data show the necessity for an antibiogram for every patient who is taking or has taken dioxidine.