AcrB-TolC efflux system is essential for macrolide resistance in Helicobacter pylori
1 Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
2 Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
3 Department of Molecular Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Research Article
GSC Advanced Research and Reviews, 2021, 09(03), 056–062.
Article DOI: 10.30574/gscarr.2021.9.3.0292
Publication history:
Received on 10 November 2021; revised on 11 December 2021; accepted on 13 December 2021
Abstract:
The prevalence of Helicobacter pylori strains resistant to macrolide is increasing worldwide. Macrolide molecules can be generally extruded by the AcrB-TolC system in bacteria. The H. pylori 26695 genome was assessed for putative translocases and the outer membrane efflux of AcrB (HP607) and TolC (HP605) proteins. We investigated the role of the AcrB-TolC efflux system in macrolide resistant (M-R) H. pylori. Both acrB- and tolC-mutant M-R strains were constructed from M-R strains by insertional inactivation of the acrB and tolC genes. The minimal inhibition concentrations (MICs) of erythromycin (EM) and clarithromycin (CLR) were determined by an agar dilution assay. To investigate the efflux ability of macrolides, intracellular accumulation of radiolabeled EM in the H. pylori 26695 strain, M-R strain, and acrB- and tolC-mutant M-R strains was measured by a liquid scintillation counter. For Post antibiotic effect (PAE), EM-treated H. pylori was diluted 1000-fold to remove antimicrobial activity. After additional 24 hours incubation, the CFU was measured. The decrease in the levels of resistance to EM and CLR was 32-fold higher for the acrB- and tolC-mutant M-R strains than the M-R strains. The intracellular EM concentration significantly increased in the acrB- and tolC-mutant M-R strains than the H. pylori 26695 and M-R strains. Diluted acrB, and tolC M-R mutant H. pylori after EM treatment was markedly reduced compared to M-R H. pylori. Our result showed that the M-R mechanism of H. pylori is significantly associated with AcrB-TolC efflux system.
Keywords:
Helicobacter pylori; AcrB; TolC; Macrolide; Drug resistant; Post antibiotic effect
Full text article in PDF:
Copyright information:
Copyright © 2021 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0
