Enhanced emergence of antibiotic-resistant pathogenic bacteria after in vitro induction with cancer chemotherapy drugs

The Journal of Antimicrobial Chemotherapy
Alexandre MeunierDidier Hocquet

Abstract

Infections with antibiotic-resistant pathogens in cancer patients are a leading cause of mortality. Cancer patients are treated with compounds that can damage bacterial DNA, potentially triggering the SOS response, which in turn enhances the bacterial mutation rate. Antibiotic resistance readily occurs after mutation of bacterial core genes. Thus, we tested whether cancer chemotherapy drugs enhance the emergence of resistant mutants in commensal bacteria. Induction of the SOS response was tested after the incubation of Escherichia coli biosensors with 39 chemotherapeutic drugs at therapeutic concentrations. The mutation frequency was assessed after induction with the SOS-inducing chemotherapeutic drugs. We then tested the ability of the three most highly inducing drugs to drive the emergence of resistant mutants of major bacterial pathogens to first-line antibiotics. Ten chemotherapeutic drugs activated the SOS response. Among them, eight accelerated the evolution of the major commensal E. coli, mostly through activation of the SOS response, with dacarbazine, azacitidine and streptozotocin enhancing the mutation rate 21.3-fold (P < 0.001), 101.7-fold (P = 0.01) and 1158.7-fold (P = 0.02), respectively. These three compounds als...Continue Reading

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Citations

May 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexsander Rodrigues Carvalho JuniorLuís Cláudio Nascimento da Silva
Apr 9, 2020·Frontiers in Microbiology·Clovis Macêdo Bezerra FilhoMaria Luiza Vilela Oliva
Aug 28, 2021·FEMS Microbiology Letters·P Dalal, D Sharma
Nov 6, 2021·International Journal of Oncology·Xing HuangBole Tian

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