Role of Penicillin-Binding Protein 1b in the Biofilm Inhibitory Efficacy of Ceftazidime Against Escherichia coli

Abstract

Penicillin-binding proteins (PBPs) play an important role in bacterial biofilm formation and are the targets of β-lactam antibiotics. This study aimed to investigate the effect of the β-lactam antibiotic ceftazidime (CAZ) at subminimal inhibitory concentration (sub-MIC) on the biofilm formation of Escherichia coli by targeting PBPs. In this study, PBP1a (encoded by mrcA), PBP1b (encoded by mrcB) and PBP3 (encoded by ftsI), which have high affinity for CAZ, were deleted from the E. coli strain. The mrcB mutant showed lower adhesion, biofilm formation and swimming motility, whereas the knockout of mrcA or ftsI had no obvious influence on the biofilm-associated indicators mentioned above. After treatment with sub-MIC of CAZ, the adhesion, biofilm formation and swimming motility of the mrcB-mutant strain were not different or were slightly reduced compared with those of the untreated group. However, sub-MIC of CAZ still significantly inhibited these biofilm-associated indicators in mrcA- and ftsI-mutant strains. In addition, consistent with the bacterial motility results, the deletion of the mrcB gene reduced the flagellar numbers and the expression of flagellar structural genes, but flagellum-related indicators in the mrcB-mutant strain treated with CAZ were similar to those in the untreated group. Bioinformatic analysis showed that CAZ binds to Lys287, Lys274, Glu281, and Arg286 in PBP1b. Taken together, these results suggest that CAZ reduced flagellar synthesis and bacterial motility by binding with PBP1b and thereby inhibited the adhesion and biofilm formation of E. coli.