Control strategies for the vertical gene transfer of quinolone ARGs in Escherichia coli through molecular modification and molecular dynamics

Abstract

This study investigates the regulation of the vertical gene transfer of quinolones’ antibiotic resistance genes (ARGs) through a combination of source modification and process control. In source prevention, 29 Escherichia coli (E. coli) DNA gyrase subunit A mutant proteins were constructed, the B-G mutant protein displayed the greatest reduction in binding effect (−25.98%). Based on this, a 3D-QSAR model was constructed, and LEV-2 and LEV-9 QNs derivatives were designed based on Levofloxacin (LEV), and their binding effect with B-G mutant protein was found be increased by 13.24% and 19.40%. The drug resistance mechanism of E. coli was explored based on molecular docking technology and protein hydrophobic interaction theory. Most of the amino acid resistance mutations changed from hydrophilic to lipophilic, which inhibited the binding of QNs to mutant protein A subunit, and further reduced the bactericidal effect of QNs. In process control, Huoxiang-Zhengqi, stroke-physiological saline solution (SPSS), and Lycium barbarum (L. barbarum) was found to be 164.82% higher than that of the blank control group. The purpose of this study is to provide a theoretical support for the joint regulation of QNs’ ARGs in organisms and the research and development on green alternatives to QNs compounds.