Gene mutations of 23S rRNA associated with clarithromycin resistance in Helicobacter pylori strains isolated from Korean patients.
Although resistance of Helicobacter pylori to clarithromycin is a major cause of failure of eradication therapies, little information is available regarding gene mutations of clarithromycin-resistant primary and secondary H. pylori isolates in Korea. In the present study, we examined gene mutations of H. pylori 23S rRNA responsible for resistance to clarithromycin. DNA sequences of the 23S rRNA gene in 21 primary clarithromycin-resistant and 64 secondary clarithromycin-resistant strains were determined by PCR amplification and nucleotide sequence analyses. Two mutations of the 23S rRNA gene, A2143G and T2182C, were observed in primary clarithromycin-resistant isolates. In secondary isolates, dual mutation of A2143G+T2182C was frequently observed. In addition, A2143G+T2182C+ T2190C, A2143G+T2182C+C2195T, and A2143G+T2182C +A2223G were observed in secondary isolates. Furthermore, macrolide binding was tested on purified ribosomes isolated from T2182C or A2143C mutant strains with [14C]erythromycin. Erythromycin binding increased in a dose-dependent manner for the susceptible strain but not for the mutant strains. These results indicate that secondary isolates show a greater variety of 23S rRNA gene mutation types than primary isolates, and triple mutations of secondary isolates are associated with A2143G+T2182C in H. pylori isolated from Korean patients.
Department of Microbiology, College of Medicine, Hanyang University, Seoul 133-791, Korea. jungmogg@hanyang.ac.kr
Jung Mogg
JM
Kim
Joo Sung
JS
Kim
Nayoung
N
Kim
Yeoung-Jeon
YJ
Kim
In Young
IY
Kim
Young Joon
YJ
Chee
Chul-Hoon
CH
Lee
Hyun Chae
HC
Jung
D017291:Clarithromycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology; D005798:Genes, Bacterial; D020459:Genes, rRNA; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007723:Korea; D008826:Microbial Sensitivity Tests; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012338:RNA, Ribosomal, 23S / Q000235:genetics*; D012270:Ribosomes / Q000187:drug effects; D017422:Sequence Analysis, DNA / Q000379:methods
D012338:RNA, Ribosomal, 23S; D004917:Erythromycin; D017291:Clarithromycin