Antibiotic resistance of through β-arrestin recruitment-induced β-lactamase signaling pathway.

Overuse and misuse of antibiotics leads to rapid evolution of antibiotic-resistant bacteria and antibiotic resistance genes. has become the most common pathogenic bacterium accountable for nosocomial infections due to its high virulence factor and general occurrence of resistance to most antibiotics. The β-lactamase signaling pathway has been suggested to be involved in antibiotic resistance against β-lactams in . In the present study, the molecular mechanism of the antibiotic resistance of was investigated and the results indicated involvement of the β-arrestin recruitment-induced β-lactamase signaling pathway. Antimicrobial susceptibility of was assessed using automated systems and extended-spectrum β-lactamase (ESBL) and β-arrestin expression levels in were analyzed by reverse-transcription quantitative PCR. β-lactam resistance in was determined using β-lactam agar screening plates. The results demonstrated that β-arrestin recruitment was increased in with antibiotic resistance (AR-.) compared with that in the native strain (NB-.). Increased production of ESBL was observed in AR-. after treatment with the β-lactam penicillin. Of note, inhibition of β-arrestin recruitment significantly suppressed ESBL expression in AR-. and in addition, genes encoding β-arrestin and ESBL were upregulated in . Restoration of endogenous β-arrestin markedly increased antibiotic resistance of to β-lactam. Knockdown of endogenous β-arrestin downregulated antibiotic resistance genes and promoted the inhibitory effects of β-lactam antibiotic treatment on growth. In conclusion, the present study identified that β-arrestin recruitment was associated with growth and resistance to β-lactams, which suggested that β-arrestin regulating ESBL expression may be a potential target for addressing antibiotic resistance to β-lactams in .