Increase in Bacterial Resistance to Antibiotics after Cancer Therapy with Platinum-Based Drugs

Аннотация

The use of platinum-based anticancer drugs is limited by both their side effects and their effect on normal microflora’s metagenome. Drugs that possess mutagenic and genotoxic properties may cause mutations in microbial genomes that contribute to the emergence of resistance to antimicrobial preparations and the development of complications after chemotherapy. The effects of cisplatin and oxaliplatin on microorganisms were studied using bacterial biosensors—E. coli strains MG1655 pKatG-lux, which reacts to the generation of hydrogen peroxide; MG1655 pSoxS-lux, which reacts to the superoxide anion radical; and the MG1655 pColD-lux strain, which detects DNA damage. The biosensor tests demonstrated high levels of genotoxicity for both drugs and some differences in the spectrum of reactive oxygen species generated. Ascorbate reduced genotoxicity of cisplatin by 41%. Nonlethal doses of cisplatin induced a three- to sevenfold increase in the frequency of the mutations that confer the resistance of E. coli to rifampicin and ciprofloxacin. Ascorbate also reduced frequency of the mutations by 65%. Thus, the effect of these drugs was probably associated with the generation of reactive oxygen species and induction of SOS response. The risk of secondary antibiotic-resistant infections may be decreased by applying antioxidants and antimutagens. At the same time, these increases may also decrease the anti-tumoral action of these compounds.