Types of 23S Ribosomal RNA Point Mutations and Therapeutic Outcomes for Helicobacter pylori

Background/Aims: Clarithromycin resistance in Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. We investigated the point mutations in the 23S rRNA genes of patients with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the point mutations. Methods: A total of 431 adult patients with H. pylori infection were recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for seven days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for seven days. H. pylori eradication rates were compared. Results: Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C). The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The overall H. pylori eradication rate was 83.7%, and the seven-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the seven-day PAC-treated nonresistance group (ITT; 55.4% (51/92) vs. 74.3% (252/339), p = 0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), p = 0.0001). Conclusions: There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori when treated with PAM for seven days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.

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Eradication of Helicobacter pylori According to 23S Ribosomal RNA Point Mutations Associated With Clarithromycin Resistance

The Journal of Infectious Diseases ◽

10.1093/infdis/jit287 ◽

2013 ◽

Vol 208 (7) ◽

pp. 1123-1130 ◽

Cited By ~ 48

Author(s):

H. J. Lee ◽

J. I. Kim ◽

D. Y. Cheung ◽

T. H. Kim ◽

E. J. Jun ◽

...

Keyword(s):

Helicobacter Pylori ◽

Ribosomal Rna ◽

Point Mutations ◽

Clarithromycin Resistance ◽

23S Ribosomal Rna

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Prevalence of Helicobacter pylori resistance to clarithromycin determined by 23S ribosomal RNA analysis in Jordan

The International Arabic Journal of Antimicrobial Agents ◽

10.3823/789 ◽

2016 ◽

Author(s):

Diab AF ◽

Diab F Hasan ◽

Nassar SS

Keyword(s):

Helicobacter Pylori ◽

Ribosomal Rna ◽

Rna Analysis ◽

23S Ribosomal Rna

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Sequence specific detection of bacterial 23S ribosomal RNA by TLR13

eLife ◽

10.7554/elife.00102 ◽

2012 ◽

Vol 1 ◽

Cited By ~ 87

Author(s):

Xiao-Dong Li ◽

Zhijian J Chen

Keyword(s):

Ribosomal Rna ◽

Single Point ◽

Point Mutations ◽

Peptide Bond ◽

Interleukin 1Β ◽

23S Rrna ◽

Sequence Specificity ◽

Bacterial Rna ◽

Microbial Infections ◽

23S Ribosomal Rna

Toll-like receptors (TLRs) detect microbial infections and trigger innate immune responses. Among vertebrate TLRs, the role of TLR13 and its ligand are unknown. Here we show that TLR13 detects the 23S ribosomal RNA of both gram-positive and gram-negative bacteria. A sequence containing 13 nucleotides near the active site of 23S rRNA ribozyme, which catalyzes peptide bond synthesis, was both necessary and sufficient to trigger TLR13-dependent interleukin-1β production. Single point mutations within this sequence destroyed the ability of the 23S rRNA to stimulate the TLR13 pathway. Knockout of TLR13 in mice abolished the induction of interleukin-1β and other cytokines by the 23S rRNA sequence. Thus, TLR13 detects bacterial RNA with exquisite sequence specificity.

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Antimicrobial Susceptibility of Canadian Isolates ofHelicobacter pyloriin Northeastern Ontario

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2015/853287 ◽

2015 ◽

Vol 26 (3) ◽

pp. 137-144 ◽

Cited By ~ 8

Author(s):

Nelson F Eng ◽

Gustavo Ybazeta ◽

Katrina Chapman ◽

Nya L Fraleigh ◽

Rebecca Letto ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Ribosomal Rna ◽

Antimicrobial Susceptibility ◽

Point Mutations ◽

Test Methods ◽

Surveillance Programs ◽

Resistant Strains ◽

H Pylori ◽

23S Ribosomal Rna

BACKGROUND:Helicobacter pyloriplays a significant role in gastritis and ulcers. It is a carcinogen as defined by the WHO, and infection can result in adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. In Canada, rates of antimicrobial resistance are relatively unknown, with very few studies conducted in the past 15 years.OBJECTIVE: To examine rates of resistance in Sudbury, Ontario, compare antimicrobial susceptibility methods and attempt to determine the molecular basis of antibiotic resistance.METHODS: Patients attending scheduled visits at Health Sciences North (Sudbury, Ontario) provided gastric biopsy samples on a volunteer basis. In total, 20H pyloriisolates were collected, and antimicrobial susceptibility testing (on amoxicillin, tetracycline, metronidazole, ciprofloxacin, levofloxacin and clarithromycin) was conducted using disk diffusion and E-test methods. Subsequently, genomic DNA from these isolates was sequenced to detect mutations associated with antimicrobial resistance.RESULTS: Sixty-five percent of the isolates were found to be resistant to at least one of the listed antibiotics according to E-test. Three isolates were found to be resistant to ≥3 of the above-mentioned antibiotics. Notably, 25% of the isolates were found to be resistant to both metronidazole and clarithromycin, two antibiotics that are normally prescribed as part of first-line regimens in the treatment ofH pyloriinfections in Canada and most of the world. Among the resistant strains, the sequences of 23S ribosomal RNA andgyrA, which are linked to clarithromycin and ciprofloxacin/levofloxacin resistance, respectively, revealed the presence of known point mutations associated with antimicrobial resistance.CONCLUSIONS: In general, resistance to metronidazole, ciprofloxacin/levofloxacin and clarithromycin has increased since the studies in the early 2000s. These results suggest that surveillance programs ofH pyloriantibiotic resistance may need to be revisited or improved to prevent antimicrobial therapy failure.

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Influence of a 23S ribosomal RNA mutation in Helicobacter pylori strains on the in vitro synergistic effect of clarithromycin and amoxicillin

BMC Research Notes ◽

10.1186/1756-0500-5-603 ◽

2012 ◽

Vol 5 (1) ◽

Cited By ~ 9

Author(s):

Türkan Sakinc ◽

Barbara Baars ◽

Nicole Wüppenhorst ◽

Manfred Kist ◽

Johannes Huebner ◽

...

Keyword(s):

Helicobacter Pylori ◽

Synergistic Effect ◽

Ribosomal Rna ◽

23S Ribosomal Rna

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Helicobacter pylori eradication according to sequencing-based 23S ribosomal RNA point mutation associated with clarithromycin resistance

10.21203/rs.2.12783/v1 ◽

2019 ◽

Author(s):

Seung In Seo ◽

Byoung Joo ◽

Jin Gu Kang ◽

Hyoung Su Kim ◽

Myoung Kuk Jang ◽

...

Keyword(s):

Point Mutation ◽

Ribosomal Rna ◽

Point Mutations ◽

23S Rrna ◽

Rrna Gene ◽

Clarithromycin Resistance ◽

Clinically Significant ◽

H Pylori ◽

23S Ribosomal Rna ◽

Significant Point

Abstract Background Clarithromycin resistance in Helicobacter pylori (H. pylori) is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. A sequencing-based method can detect more point mutations than a polymerase chain reaction (PCR)-based method. We investigated the point mutations in the 23S rRNA genes of patients infected with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the identified clinically significant point mutations. Methods A total of 431 adult patients with H. pylori infection were retrospectively recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for 7 days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for 7 days. H. pylori eradication rates were compared between the two groups. Results Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C), while all the other mutations were considered clinically insignificant. The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The H. pylori eradication rate in the overall group of patients was 83.7%, and the 7-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the 7-day PAC-treated nonresistance group [ITT; 55.4% (51/92) vs. 74.3% (252/339), P=0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), P=0.0001]. Conclusions There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori as identified by the sequencing of point mutations in the 23S rRNA gene when treated with PAM for 7 days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.

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