Resistance mechanisms ofHelicobacter pyloriand its dual target precise therapy

Gong, Yuehua; Yuan, Yuan

doi:10.1080/1040841x.2017.1418285

Cited by 64 publications

(70 citation statements)

References 163 publications

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“…30 Therefore, the 87 and 91 mutations might not only affect protein structure but also directly impair the binding between protein and DNA Hideki Mori et al showed double-mutate strain (N87 and D91 or N87 and A88) in gyrA evoked high-level resistance in H. pylori. 36 The MIC values of antibiotic-resistant strains with gyrA mutation were significantly higher than those of nonmutant strains, indicating that gyrA mutation was associated with high LVXresistant level. 33 Regarding 99 and 143 sites, our results also demonstrated the binding with LVX were weakened after mutation.…”

Section: Discussionmentioning

confidence: 91%

“…Seck et al also found no gyrA mutation in some LVX-resistant strains, 34 suggesting other resistance-related mechanisms such as efflux pump, 35 membrane permeability, autophagy, globular transformation, and even new resistant genes. 36 The MIC values of antibiotic-resistant strains with gyrA mutation were significantly higher than those of nonmutant strains, indicating that gyrA mutation was associated with high LVXresistant level. Hideki Mori also displayed that the significant difference of the MICs of sitafloxacin between gyrA mutation-negative and -positive H. pylori strains.…”

Section: Discussionmentioning

confidence: 91%

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Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

et al. 2019

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To explore the mutation characteristics of H. pylori resistance-related genes to antibiotics of clarithromycin (CAM), levofloxacin (LVX) and metronidazole, 23SrRNA, gyrA, gyrB, rdxA, and frxA genes were amplified and sequenced, respectively. Molecular docking study was performed to explore molecular interactions between chemotherapeutic agents and target proteins. In the CAM-resistant strains, the mutation rate in site A2143G was 74.2% (n = 23). The interactions in sites of G1949A, C1953T, and G2211T with CAM were weaker after mutation. In the LVX-resistant strains, the mutation rates in 87 (N to K/I) and 91 (D to N/Y/G) of gyrA were 28.6% (n = 16) and 12.5% (n = 7), respectively. We could infer by docking studies that N87 K/I, D91Y/G/N, D99N, and D143E mutations in GyrA protein all had weakened interaction with LVX. The mutation types of RdxA protein consisted of protein truncation caused by premature stop codons (n = 26, 33.3%), frameshift mutations (n = 8, 10.3%), FMN-binding sites (n = 16, 20.5%), and the others (n = 11, 14.1%).Docking analysis showed that some mutations in those four types of RdxA protein could reduce interaction with MNZ, and play a significant role in antibiotic resistance. What's more, we performed natural transformation with some of these mutated DNA fragments to see if they really impact susceptibility to antibiotics. Our study suggested that in addition to the reported mutation sites, H. pylori antibiotic resistance in this region may also be associated with changes in some new sites. Our study provides novel ideas and methods for the identification of H. pylori resistancerelated mutations, and also clues and basis for further investigation on specific molecular mechanism.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

et al. 2019

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“…The genotypic determination of antimicrobial resistance has made possible the elucidation of the molecular mechanisms of H. pylori resistance to antimicrobials such as clarithromycin, tetracycline, metronidazole, among others [22][23][24][25][26][27]. Resistance to clarithromycin has resulted from 3 points mutations A2142G, A2142C, and A2143G in 23S rDNA in the gene encoding the peptidyl transferase enzyme especially in the V domain (mutations too named like A2146C, A2146G, and A2147G) [28].…”

Section: Introductionmentioning

confidence: 99%

Surveillance of the Antimicrobial Resistance Rates of Helicobacter pylori Ten Years Later in the Western Central Region, Colombia

Bedoya-Gómez

Aldana

Moncayo

et al. 2019

Dig Dis

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Background: Helicobacter pylori is a bacterium associated with gastroduodenal disease and gastric cancer. Empirical therapy in the treatment of H. pylori infection increases the risk of apparition of antimicrobial drug resistance. In a previous report, in H. pylori clinical isolates, resistance rates to commonly used antimicrobial drugs were as follows: metronidazole 82%, clarithromycin 3.8%, and amoxicillin 1.9%. The aim was to establish the variation of resistance rates and the detection of H. pylori genetic mutations isolated from dyspeptic patients. Methods: Antimicrobial susceptibility profiles were performed by the E-test method for metronidazole, clarithromycin, amoxicillin, and tetracycline in 61 clini-cal isolates. Sequencing was performed to detect mutations associated with resistance to clarithromycin. Results: According to our results, resistance rates found in the 61 isolates were 78.60% for metronidazole and 8.20% for clarithromycin. None of the studied isolates had resistance to tetracycline and amoxicillin. Secondary resistance rates displayed an increase when compared to primary rates for metronidazole (87.50 vs. 77.35%) and for clarithromycin (25.66 vs. 5.66%). Of 5 isolates resistant to clarithromycin, 3 had the A2143G mutation. By comparing the results in this work with previous reports, antimicrobial drug resistance rates did not show major modifications for metronidazole, amoxicillin, and tetracycline during the last 10 years. For clarithromycin, the resistance rate showed a moderate increase; nevertheless, it remains low (< 15%) and this change was not statistically significant. Conclusion: Together, all findings in this work indicate that these antimicrobial drugs can still be used as first line of defense on infected patients living in this region of the country.

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“…48,49 The goal of medicine precision is identify which regimen is best for an individual patient. 53 Thus, our results suggest in the future that personalized therapy could be ideal for H pylori eradication under controlled conditions, considering personalized medicine could avoid an increase in adverse effects, such as lack of patient's compliance and increase in antibiotic resistance.…”

Section: Discussionmentioning

confidence: 72%

Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first‐line triple therapy

2019

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Background Triple therapy efficacy against Helicobacter pylori is low worldwide, and thus, alternatives must be sought to improve eradication. The aim of the present study was to determine CYP2C19 genetic polymorphism effect on H pylori eradication. Methods A randomized, single‐blinded clinical trial including 133 participants was carried out. H pylori infection was confirmed by histologic and microbiologic test. Antibiotic susceptibility to amoxicillin and clarithromycin was performed. CYP2C19 polymorphisms *1, *2, and *3 were analyzed by real‐time PCR (Roche ®), and nested PCR for CYP2C19*17 polymorphisms. Participants were randomized into two groups for different H pylori therapies, one with standard omeprazole doses and another with omeprazole doses depending on CYP2C19 polymorphism. H pylori eradication was verified by stool antigen tests (Meridian ®). Results The most common CYP2C19 polymorphism was *1/*1 in 54.9% of the participants followed by *17/*17 in 21.1%. Triple therapy efficacy with standard omeprazole doses versus personalized therapy based on CYP2C19 polymorphism by ITT analysis was 84% (95% CI: 0.73‐0.91) vs 92.2% (95% CI: 0.82‐0.97) (P = 0. 14), respectively. The efficacy by PP analysis was 92.1% (95% CI: 0.82‐0.97) vs 100% (95% CI: 0.92‐0.01) (P = 0.027), respectively. Conclusions The most frequent polymorphism was extensive PPI metabolizers (62.4%). Effectiveness of guided therapies by susceptibility test was good, yet they can be further improved by customized therapy based on CYP genotype. Therefore, high PPI (80 mg/d) doses are recommended for H pylori eradication therapies in Colombia. ClinicalTrials.gov ID: NCT03650543.

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Resistance mechanisms ofHelicobacter pyloriand its dual target precise therapy

Cited by 64 publications

References 163 publications

Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

Surveillance of the Antimicrobial Resistance Rates of <b><i>Helicobacter pylori</i></b> Ten Years Later in the Western Central Region, Colombia

Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first‐line triple therapy

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