Antibiotic resistance of Klebsiella�pneumoniae through β-arrestin recruitment-induced β-lactamase signaling pathway

Abstract

Overuse and misuse of antibiotics leads to rapid evolution of antibiotic-resistant bacteria and antibiotic resistance genes. Klebsiella pneumoniae 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 Klebsiella pneumoniae. In the present study, the molecular mechanism of the antibiotic resistance of Klebsiella pneumoniae was investigated and the results indicated involvement of the β-arrestin recruitment-induced β-lactamase signaling pathway. Antimicrobial susceptibility of Klebsiella pneumoniae was assessed using automated systems and extended-spectrum β-lactamase (ESBL) and β-arrestin expression levels in Klebsiella pneumoniae were analyzed by reverse-transcription quantitative PCR. β-lactam resistance in Klebsiella pneumoniae was determined using β-lactam agar screening plates. The results demonstrated that β-arrestin recruitment was increased in Klebsiella pneumoniae with antibiotic resistance (AR-K.P.) compared with that in the native Klebsiella pneumoniae strain (NB-K.P.). Increased production of ESBL was observed in AR-K.P. after treatment with the β-lactam penicillin. Of note, inhibition of β-arrestin recruitment significantly suppressed ESBL expression in AR-K.P. and in addition, genes encoding β-arrestin and ESBL were upregulated in Klebsiella pneumoniae. Restoration of endogenous β-arrestin markedly increased antibiotic resistance of Klebsiella pneumoniae to β-lactam. Knockdown of endogenous β-arrestin downregulated antibiotic resistance genes and promoted the inhibitory effects of β-lactam antibiotic treatment on Klebsiella pneumoniae 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 Klebsiella pneumoniae.

TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

“…It is well known that K. pneumoniae is a common cause of severe infections including pneumonia, endophthalmitis and meningitis [25]. Because of its hypervirulence and general occurrence of resistance Viruses 2020, 12,192 7 of 12 to most antibiotics, in recent years infections caused by K. pneumoniae have become progressively difficult to treat [26,27]. In this study, we examined the antibacterial activity of TSPphg against nine different antibiotic-resistant strains of K. pneumoniae that are exceedingly hard to deal with in clinic practice.…”

Isolation and Characterization of a Novel Klebsiella pneumoniae N4-like Bacteriophage KP8

“…The cps cluster has a mosaic structure with a group of six conserved genes (galF, orf2, wzi, wza, wzb, and wzc) at the 5' end, which may be used for the molecular serotyping of K. pneumoniae strains [4,5]. Clinical isolates of K. pneumoniae, causing severe nosocomial infections, often possess multiple antibiotic resistances [6][7][8]. During the last decades, the prevalence of extended-spectrum β-lactamases (ESBL) producing K. pneumoniae has dramatically increased worldwide and K. pneumoniae is mostly associated with the dissemination of ESBLs and other horizontally transmissible resistance genes in most parts of the world [6,9].…”

Characteristics, Patterns of Pathogens, and Antibiotics Resistance of Bacterial Meningitis at Rsup Dr. Mohammad Hoesin Palembang

“…Klebsiella is the most common bacterial pathogen that causes nosocomial infections due to various virulence factors and resistance to many antibiotics. 17 Meanwhile, according to Jawetz et al, E. coli and streptococci are the main causes of meningitis, especially in infants. E. coli is the cause of about 40% of cases of neonatal meningitis.…”

“…The resistance mechanism is mediated by the loss of porin in the cytomembranes, production of ESBL, carbapenemases and even metallo-β-lactamases to increase antibiotic resistance. 17,25…”