Cephalosporin Exposure Influences Transcriptional Response of mrcA and mrcB in Escherichia coli Harbouring bla_CTX−M

The widespread dissemination of extended-spectrum β-lactamase (ESBL)-producing strains of Escherichia coli is a matter of serious concern. The bla_CTX−M genes are well known for imparting resistance to β-lactams. The mrcA and mrcB genes, encoding penicillin-binding proteins involved in bacterial cell wall synthesis, are targets for cephalosporin binding. This study aimed to identify the ESBL activity-associated genes, their network, and examine their transcriptional expression in E. coli isolates to assess their potential as biomarkers. A total of 172 E. coli isolates were tested for antibiotic susceptibility, and most were found to be susceptible to gentamicin. On performing polymerase chain reaction, bla_TEM and bla_CTX−M genes were detected. Gene network analysis was employed to identify the endogenous genes, mrcA and mrcB, in E. coli harbouring bla_CTX−M. Both clinical isolates and their respective transformants were used for transcriptional analysis of the endogenous genes, with and without cephalosporin stress. Both cefotaxime and ceftazidime induced ~ 3.4- and ~ 10-fold changes in mrcA and ~ 8.8- and ~ 4.2-fold changes in mrcB, respectively, in clinical isolates. However, their responses were antibiotic-specific. The transcriptional expression of mrcA in transformants was induced by cefotaxime and experienced a fold-change of ~ 8.6, while ceftazidime markedly suppressed the expression of mrcB. The induced transcriptional responses of both mrcA and mrcB upon exposure to cefotaxime and ceftazidime suggest the possibility of these endogenous genes serving as reporters for determining cephalosporin resistance in E. coli.