Antioxidant molecules as a source of mitigation of antibiotic resistance genes dissemination
Escherichia coli is the most commonly identified human pathogen, and a prominent microorganism of the gut microbiota. Acquired resistance to antibiotics in that species is mainly driven by horizontal gene transfer, and mainly by plasmid acquisition. The main concern nowadays corresponds to the acquisition of extended-spectrum ß-lactamases of the CTX-M-type in E. coli, a worldwide observed phenomenon. Plasmids encoding CTX-M enzymes are of different scaffolds, and conjugate at different frequencies. Here we showed that the conjugation rates of several plasmid types encoding broad-spectrum ß-lactamases are increased when the E. coli donor strain is exposed to sub-inhibitory concentrations of diverse orally-given antibiotics, including fluoroquinolones such as ciprofloxacin and levofloxacin, but also trimethoprim, and nitrofurantoin. This study provided insights into underlying mechanisms leading to increase plasmid conjugation frequency in relation with DNA synthesis inhibitors-type antibiotics, involving reactive oxygen species (ROS) production and probably increased expression of genes involved in the SOS response. Furthermore, we showed that some antioxidant molecules currently approved for unrelated clinical uses such as edaravone, p-Coumaric acid and N-acetylcysteine may antagonize the inducibility effect of antibiotics in term of increased plasmid conjugation rates. These results suggest that several antioxidative molecules might be used in combination with those “inducer” antibiotics to mitigate the unwanted increased resistance plasmid dissemination.