Klebsiella pneumoniae presents antimicrobial drug resistance for β‑lactam through the ESBL/PBP signaling pathway

Abstract

Overuse and misuse of antibiotics leads to antibiotic resistance which has become a significant public health concern. <i>Klebsiella pneumoniae</i> is the most common pathogenic bacteria underlying nosocomial infections due to the expression of virulence factors and occurrence of antibiotic resistance. Evidence indicates that β-lactamase is involved in the antibiotic resistance of <i>Klebsiella pneumoniae</i> to β-lactam antibiotics. The aim of the present study was to investigate the association between the molecular biological mechanisms of antibiotic resistance of <i>Klebsiella pneumoniae</i> and extended-spectrum β-lactamase (ESBL). In order to assess temporal trends in prevalence and antimicrobial susceptibility, <i>Klebsiella pneumoniae</i> bacteria were isolated and the ESBL expression level was analyzed. Susceptibility tests were performed using automated systems. The β-lactam-resistance in <i>Klebsiella pneumoniae</i> was assessed by the β-lactam agar screen plate and respective MIC values were evaluated using E-test strips. The confirmatory disk diffusion methods were applied for phenotypic identification of the ESBL production of <i>Klebsiella pneumoniae</i>. The results showed that <i>Klebsiella pneumoniae</i> bacteria exhibited higher ESBL production after treatment with β-lactam compared to the control. The ESBL gene expression was upregulated in <i>Klebsiella pneumoniae</i> after treatment with β-lactam. Results identified that penicillin-binding proteins (PBPs) were associated with the growth and resistance to β-lactams. Zinc finger nuclease markedly inhibited the antibiotic resistance of <i>Klebsiella pneumoniae to</i> β-lactam. PBP knockdown abolished the inhibitory effects of zinc finger nuclease on the growth of <i>Klebsiella pneumonia</i> <i>e</i> induced by β-lactam antibiotic treatment. In conclusion, these results suggest that the resistance of <i>Klebsiella pneumoniae</i> bacteria <i>to</i> antimicrobial drugs is through the ESBL signaling pathway, which indicates that ESBL may be a potential target for abolishing resistance to β-lactam.