Discovery of a Novel Mutation in DNA Gyrase and Changes in the Fluoroquinolone Resistance of Helicobacter pylori over a 14-Year Period: A Single Center Study in Korea

Abstract

The efficacy of fluoroquinolone-based eradication therapy largely depends on the fluoroquinolone resistance of H. pylori. The aim of this study was to investigate the changes in the primary resistance rate of H. pylori to fluoroquinolone and the mechanism of resistance in Korea. A total of 153 strains and 48 strains of H. pylori were isolated at a tertiary hospital in 2005/2006 and 2017/2018, respectively. The minimum inhibitory concentrations (MICs) of fluoroquinolone were determined by the serial 2-fold agar dilution method. DNA sequences in the quinolone resistance-determining regions of gyrA/gyrB were analyzed in resistant strains. Subsequent natural transformation study was performed to determine the association between gyrase mutation and resistance. The resistance rates increased from 19.0% (29/153) to 43.8% (21/48) both for levofloxacin and moxifloxacin. The MIC values for resistant strains increased from 2–8 µg/mL to 4–16 µg/mL over time. Mutation of gyrA was detected in 93.1% (27/29) and 100% (21/21) among the resistant strains in both periods, respectively. A novel Gly-85 mutation of gyrA was found and confirmed to be associated with fluoroquinolone resistance. Fluoroquinolone resistance rate of H. pylori has markedly increased over time in Korea. The resistance is mostly due to the point mutation of gyrA. Fluoroquinolone-containing regimens should be carefully selected in Korea, considering the increasing fluoroquinolone resistance.

Secondary Antibiotic Resistance, Correlation between Genotypic and Phenotypic Methods and Treatment in Helicobacter pylori Infected Patients: A Retrospective Study

“…LEV resistance rate of 11% was detected in Morocco by Bouihat et al [ 23 ] in a multicenter study of patients who had never been treated previously. Interestingly a recent article [ 27 ] dealing with a study in Korea reports a new mutation of gyrA (a novel Gly-85 mutation of gyrA ) different from those we have examined in our research, conferring resistance to fluoroquinolones. In this case, the authors found that the resistance rates increased from 19.0% to 43.8% both for levofloxacin and moxifloxacin.…”

Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from Helicobacter pylori Next Generation Sequencing Data

“…The main antibiotics used for H. pylori eradication, the resistance mechanisms and the main resistance biomarkers are briefly reviewed below and are summarized in Table 2. [156,159,[168][169][170] * Exemplificative studies targeting the mentioned biomarker are referred.…”

“…The most common mutations occur on the quinolone resistance-determining region (QRDR) of gyrA affecting codons 91 and 87 of the gyrA product, more specifically D91 to G [149,159,165,168], N [150,165,168,169,200] or Y [150,165,168] and N87K [150,159,165,168,201]. Despite this, changes in other codons of both gyrA, and, less frequently, gyrB products were, and continue to be, frequently reported, although the impact of some of them on antibiotic resistance is not yet well established [168,171,200]. Alternative mechanisms have not been described but were suggested to exist [165,168,171].…”

“…Despite this, changes in other codons of both gyrA, and, less frequently, gyrB products were, and continue to be, frequently reported, although the impact of some of them on antibiotic resistance is not yet well established [168,171,200]. Alternative mechanisms have not been described but were suggested to exist [165,168,171].…”

“…For antibiotic-resistance in specific, phenotypic evaluation procedures, such as the agar dilution method-the gold standard-and E-tests are still widely used [213], and are often the starting point for the identification of resistance-conferring mutations [168,176,187]. However, these methods, apart from being time-consuming, costly and technically demanding, are widely subjective and culture-dependent.…”