Insight into the impacts and mechanisms of ketone stress on the antibiotic resistance in Escherichia coli

Accumulation of toxic organic has posed a substantial pressure on the proliferation of bacterial resistance. While aromatic organics have been demonstrated to enhance the antibiotic resistance in bacteria, no information is yet available on the effects of non-aromatic organics on the variations of bacterial resistance. Here, we investigated the effects of a typical ketone (i.e., methylisobutanone (MIBK)) on the variations of antibiotic resistance in Escherichia coli (E. coli). The results showed that the growth of resistant E. coli under environmental concentration of 50 mu g/L MIBK was firstly inhibited as explained by the transient disruption in the cell membrane and then recovered possibly due to the reactive oxygen species. Exposure to 50 mu g/L MIBK gradually raised the abundance of representative resistance gene (ampR) in E. coli. In contrast, the high concentration of 50 mg/L MIBK continuously inhibited the growth of resistant E. coli by disrupting cell membrane and notably promoted the proliferation of ampR through enhancing the horizontal transformation and up-regulating the expression of efflux pump gene. These findings provided the first evidence for the evolution of bacterial resistance in response to ketone organics.