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

Jian-Jun Tao; Shao-Hua Li; Jia-Han Wu; Xuan-Xian Peng; Hui Li

doi:10.3389/fmicb.2023.1276954

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

Front Microbiol. 2023 Nov 6:14:1276954. doi: 10.3389/fmicb.2023.1276954. eCollection 2023.

Authors

Jian-Jun Tao¹, Shao-Hua Li¹, Jia-Han Wu¹, Xuan-Xian Peng^{1

2

3}, Hui Li^{1

2}

Affiliations

¹ State Key Laboratory of Bio-Control, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
² Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
³ Guangdong Litai Pharmaceutical Co. LTD, Jieyang, China.

Abstract

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 (Δpts-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 Δpts-P compared with K12, and with glucose as controls.

Results: Δpts-P exhibits the resistance to β-lactams and aminoglycosides but not to quinolones, tetracyclines, and macrolide antibiotics. Inactivated pyruvate cycle was determined as the most characteristic feature in Δpts-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 β-lactams-, aminoglycosides-, quinolones-mediated killing in K12, which was inhibited by carbonyl cyanide 3-chlorophenylhydrazone. Exogenous glucose did not elevated ROS in K12 and Δpts-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.

Keywords: Escherichia coli; PTS; antibiotic resistance; glucose; reprogramming metabolomics; the pyruvate cycle.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by grants from National Natural Science Foundation of China (31770045), Science and Technology Plan Project of Guangzhou (201904020042), Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (No. 311020006).