Escherichia coli strain:K12 MG1655 Genome sequencing. Escherichia coli strain:K12 MG1655

The extensive clinical use of cephalosporins releases into the environment in low concentrations, which select for highly resistant bacteria, risking the evolution and spread of antibiotic resistance. Therefore, it is critical to study antibiotic resistance evolution in bacteria exposed to cephalosporin at environmental concentrations. In this study, model strain Escherichia coli K12 MG1655 was respectively subcultured under eight cephalosporin stresses at 25 ppb for 60 days. Evolutionary clones under eight stressors were resequenced and showed evolutionary heterogeneity in either genotypes or multidrug resistance levels. Through constructing a QSPR model based on molprint2D fingerprints, the R2 group of cephalosporin was performed to play an essential role in affecting antibiotic resistance evolution. Interestingly, hisG mutant promoted up to 128 fold changes in MDR levels. The gene hisG knockout strain became more sensitive to lactam antibiotics than the wild type strain. Furthermore, we revealed that the hisG mutant confers MDR by the novel resistance mechanism, fatty acids degradation, which alters the cell metabolic response for better adaptation. This finding provides a fundamental insight into the targeted removal technology of cephalosporins. Moreover, the discovery of the resistance-related gene and its novel regulatory pathway are conducive to identifying new resistance mechanisms and risk prevention of antibiotic resistance evolution.