Characterisation of point mutations in domain V of the 23S rRNA gene of clinical Helicobacter pylori strains and clarithromycin-resistant phenotype in central Vietnam

Tran, Van Huy; Ha, Thi Minh Thi; Le, Phan Tuong Quynh; Phan, Trung Nam; Tran, Thi Ngoc Anh

doi:10.1016/j.jgar.2018.09.012

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…The PCR-RFLP is still being used, an accurate, rapid, and low-cost method. 22,23 Both techniques showed that all phenotypic clarithromycin-resistant isolates had either A2142G, A2143G, or A2143C mutations. The prevalence of A2142G was 36% (21/58), A2143G 10% (6/58), and A2143C was 1.7% (1/ 58).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Domain V Mutations in Clinical Isolates of Helicobacter pylori in Pakistan and Their Effect on Clarithromycin MIC

Anis¹,

Niaz²

2021

IDR

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Purpose: Clarithromycin is commonly prescribed for H. pylori infection. Domain V mutations are responsible for clarithromycin resistance. This study was aimed to characterize the clarithromycin resistance and its associated mutations in clinical isolates of H. pylori in Pakistan. Materials and Methods: Infection was diagnosed in 93 patients' biopsies using culture, rapid urease test, 16S rRNA, and vacA gene multiplex PCR. Clarithromycin resistance was assessed by the agar dilution method. Mutations were detected by PCR-RFLP using 46 (1.4 kb) domain V fragments. Sequencing was executed for 13 domain V fragments, of which 12 showed unusual amplicon size (1.2 kb) and 01 had a new MboII RFLP pattern. Results: A total of 48 (83%) strains were obtained from 58 (62.3%) PCR H. pylori-positive samples. Resistance (MIC ≥ 0.001 mg/mL) and intermediate resistance phenotype (MIC = 0.0005 mg/mL) was observed in 22 (46%), and 10 (21%) isolates, respectively. The primary resistance was found in 23 (39.6%) samples. PCR-RFLP detected A2142G, A2143G, and double mutations in 19, 04, and 01 resistant strain, respectively. Sequencing of 10 amplicons obtained from intermediated resistant strains and 03 amplicons from resistant strains showed 138 new mutations. Among them, T2182C was also seen in 04 intermediated resistant isolates, whereas A2142G, A2143G, and A2143C were observed in resistant isolates. The new MboII RFLP pattern in an intermediated resistant strains was due to A1761G mutation. Conclusion: H. pylori domain V mutations showed extensive diversity. Multiple mutations in domain V may give endurance to H. pylori against clarithromycin. Further investigations on the molecular mechanism of antibiotic resistance in H. pylori seem crucial at this stage.

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Section: Discussionmentioning

confidence: 99%

Characterization of Domain V Mutations in Clinical Isolates of Helicobacter pylori in Pakistan and Their Effect on Clarithromycin MIC

Anis¹,

Niaz²

2021

IDR

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“…Clarithromycin resistance is mediated by mutations in the 23S rRNA gene that reduce the affinity of clarithromycin for the 23S ribosomal component and inhibit clarithromycin activity against H. pylori [ 25 ]. The most commonly reported mutations include 2143A>G, 2142A>G, and 2142A>C [ 12 , 13 , 15 , 26 , 27 ]. Several other mutations have been recognized, such as 2182T>C, 2183T>C, 2223A>G, 2717T>C, 2245T>C, and 2116A>G (corresponding to nucleotide locations at 2186, 2187, 2227, 2722, 2249, and 2120 in this study), but their clinical relevance remains controversial [ 12 , 16 , 17 , 23 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several other mutations have been recognized, such as 2182T>C, 2183T>C, 2223A>G, 2717T>C, 2245T>C, and 2116A>G (corresponding to nucleotide locations at 2186, 2187, 2227, 2722, 2249, and 2120 in this study), but their clinical relevance remains controversial [ 12 , 16 , 17 , 23 , 28 , 29 , 30 , 31 , 32 ]. Several reports suggested that 2143A>G is responsible for clarithromycin resistance and is associated with eradication failure [ 12 , 23 , 27 , 33 , 34 ]. In a previous study, 2143A>G mutation was found only in clarithromycin-resistant strains, and the presence of 2143A>G was correlated with the efficacy of eradication therapy [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains

Gong

Ahn

Kim

et al. 2020

JCM

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Background: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. Methods: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. Results: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. Conclusions: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.

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“…Moreover, the H. pylori strains analyzed here carried new nucleotide substitutions in or outside of domain V as follows: A1410G, C1707T, A2167G, C2248T+G2287A, and C2922T. The G2287A mutation was detected in Vietnam [ 34 ]. Further studies are therefore required to explain the variety of antibiotic-resistance determinants in the 23S rRNA gene.…”

Section: Discussionmentioning

confidence: 99%

High Antibiotic Resistance of Helicobacter pylori and Its Associated Novel Gene Mutations among the Mongolian Population

et al. 2020

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Mongolia has a high prevalence of Helicobacter pylori infection and the second highest incidence of gastric cancer worldwide. Thus, investigating the prevalence of antibiotic resistance and its underlying genetic mechanism is necessary. We isolated 361 H. pylori strains throughout Mongolia. Agar dilution assays were used to determine the minimum inhibitory concentrations of five antibiotics; amoxicillin, clarithromycin, metronidazole, levofloxacin, and minocycline. The genetic determinants of antibiotic resistance were identified with next-generation sequencing (NGS) and the CLC Genomics Workbench. The resistance to metronidazole, levofloxacin, clarithromycin, amoxicillin, and minocycline was 78.7%, 41.3%, 29.9%, 11.9% and 0.28%, respectively. Multidrug resistance was identified in 51.3% of the isolates investigated which were further delineated into 9 antimicrobial resistance profiles. A number of known antibiotic resistance mutations were identified including rdxA, frxA (missense, frameshift), gyrA (N87K, A88P, D91G/N/Y), 23S rRNA (A2143G), pbp1A (N562Y), and 16S rRNA (A928C). Furthermore, we detected previously unreported mutations in pbp1A (L610*) and the 23S rRNA gene (A1410G, C1707T, A2167G, C2248T, and C2922T). The degree of antibiotic resistance was high, indicating the insufficiency of standard triple therapy in Mongolia.

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Characterisation of point mutations in domain V of the 23S rRNA gene of clinical Helicobacter pylori strains and clarithromycin-resistant phenotype in central Vietnam

Cited by 15 publications

References 23 publications

Characterization of Domain V Mutations in Clinical Isolates of Helicobacter pylori in Pakistan and Their Effect on Clarithromycin MIC

Characterization of Domain V Mutations in Clinical Isolates of Helicobacter pylori in Pakistan and Their Effect on Clarithromycin MIC

Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains

High Antibiotic Resistance of Helicobacter pylori and Its Associated Novel Gene Mutations among the Mongolian Population

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