Genetic resisters to antibiotics in Escherichia coli arise from the antibiotic-surviving population containing three reactive oxygen species.

Abstract

Antibiotic-exposed bacteria acquire genetic mutations and emerge as antibiotic-resistant clones that thwart treatment of bacterial diseases. Genome-wide mutations are inflicted by the reactive oxygen species (ROS), hydroxyl radical, formed in most of the antibiotic-exposed bacteria. Hydroxyl radical is generated through the Fenton reaction of Fe (II) with H2O2, which is formed by the dismutation of superoxide. This implied that antibiotic-exposed bacteria would contain these three ROS, promoting resister generation. In the present study, we examined Escherichia coli exposed independently to gentamicin and moxifloxacin for the presence of the three ROS and consequential emergence of genetic resisters to the antibiotics. Here we show that the three ROS are formed in E. coli exposed independently to bactericidal concentrations of gentamicin and moxifloxacin for a prolonged duration. Resisters to these antibiotics were found to emerge from the respective antibiotic-surviving population. The antibiotic-unexposed cultures did not show these responses. The Gram-positive ESKAPE pathogen, Staphylococcus aureus, also showed a response similar to that of E. coli upon prolonged exposure to bactericidal concentrations of rifampicin and moxifloxacin. The similar responses of E. coli and S. aureus to antibiotics indicated a common mechanism of ROS generation in the emergence of resisters against antibiotics.