Formation of A2143G mutation of 23S rRNA in progression of clarithromycin resistance in Helicobacter pylori 26695.
The aim of this work was to investigate the link between 23S rRNA mutation and clarithromycin (CLR)-resistant Helicobacter pylori (H. pylori). CLR-resistant (CLRr) H. pylori strains were selected from the parent strain, H. pylori 26695, using medium containing CLR. Point mutations of 23S rRNA were analyzed by denaturing high-performance liquid chromatography and sequencing and restriction fragment length polymorphism (RFLP). Protein profiles of these strains were obtained by surface-enhanced laser/desorption ionization time-of-flight mass spectrometry technology. Two phenotype-stable L-CLRr resistant strains (MIC 8, 10 microg/ml) and two subsequent CLRr strains (MIC 32 microg/ml) were obtained. An A2143G mutation of 23S rRNA was detectable in two CLRr strains, but in neither the CLRs parent strain nor the L-CLRr strains. Four clinical CLRr H. pylori strains were obtained from 41 Chinese H. pylori isolates. The A2143G mutation was observed in all four CLRr isolates, but not in the six analyzed CLRs ones. Protein profiling showed that the pattern of protein expression was changed from the CLRs parent strain to the L-CLRr strains and then to the CLRr strains progressively. The formation of A2143G mutations of 23S rRNA might be a late event in the development of CLR-resistance of H. pylori 26695. Early events related to alteration of the pattern of protein expression might be involved in the development of CLR-resistance too.
Shen
Jing
J
Peking University School of Oncology and Beijing Institute for Cancer Research, Beijing, China.
Zhang
Jian-Zhong
JZ
Ke
Yang
Y
Deng
Dajun
D
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology*; D018450:Disease Progression; D024881:Drug Resistance, Bacterial; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012338:RNA, Ribosomal, 23S / Q000235:genetics*
D000900:Anti-Bacterial Agents; D012338:RNA, Ribosomal, 23S; D017291:Clarithromycin