Genetic basis for metronidazole and clarithromycin resistance in Helicobacter pylori strains isolated from patients with gastroduodenal disorders

The aim of this study was to evaluate the antimicrobial resistance and genetic basis for metronidazole (Mtz) and clarithromycin (Cla) resistance in strains of , isolated from patients with gastroduodenal disorders. A total of 157 . isolates (from 22 gastric cancer, 38 peptic ulcer disease, and 97 non-ulcer dyspepsia patients) were analyzed for drug susceptibility to Mtz and Cla, by gradient diffusion test (E-test, MAST). The PCR and sequence analysis of the and for Mtz-resistant strains and the for Cla-resistant strains were used to determine the genetic basis of drug resistance in strains. Increased expression of homologous genes ( ) that upregulates efflux pump activity was determined in multidrug-resistant (MDR) strain of by real-time PCR technique. Among 157 . isolates, 32 (20.4%) strains were resistant to at least one of the antimicrobial agents. The highest resistance rate was attributed to Mtz (n=69, 43.94%). Among the resistant strains of , 15 cases (9.55%) were detected as MDR. Mutations in the (85.5%) and A2143G point mutations (63.1%) in the were the most common cause of resistance to Mtz and Cla in strains of , respectively. In MDR strains, the mutation and A2143G-point mutation in the were the most abundant mutations responsible for drug resistance. The relative expression of in MDR strains (mean 3.706) was higher than the susceptible strains (mean 1.07). Mutational inactivation and efflux pump overexpression are two mechanisms that increase the resistance to antimicrobial agents and the rate of MDR strains. In Iran, the mutations of and in Mtz-resistant strains and A2143G and A2142G of the in Cla-resistant strains were significant. The screening for these mutations could help to prevent antibiotic resistance, and to determine the most effective anti- drugs.