pts promoter influences antibiotic resistance via proton motive force and ROS in Escherichia coli

Introduction: Glucose level is related to antibiotic resistance. However, underlying mechanisms are largely unknown.Methods: Since glucose transport is performed by phosphotransferase system (PTS) in bacteria, pts promoter-deleted K12 (Delta pts-P) was used as a model to investigate effect of glucose metabolism on antibiotic resistance. Gas chromatography-mass spectrometry based metabolomics was employed to identify a differential metabolome in Delta pts-P compared with K12, and with glucose as controls.Results: Delta pts-P exhibits the resistance to beta-lactams and aminoglycosides but not to quinolones, tetracyclines, and macrolide antibiotics. Inactivated pyruvate cycle was determined as the most characteristic feature in Delta pts-P, which may influence proton motive force (PMF), reactive oxygen species (ROS), and nitric oxide (NO) that are related to antibiotic resistance. Thus, they were regarded as three ways for the following study. Glucose promoted PMF and beta-lactams-, aminoglycosides-, quinolones-mediated killing in K12, which was inhibited by carbonyl cyanide 3-chlorophenylhydrazone. Exogenous glucose did not elevated ROS in K12 and Delta pts-P, but the loss of pts promoter reduced ROS by approximately 1/5, which was related to antibiotic resistance. However, NO was neither changed nor related to antibiotic resistance.Discussion: These results reveal that pts promoter regulation confers antibiotic resistance via PMF and ROS in Escherichia coli.