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Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA.

Authors
 So Yeong Kim  ;  Young Min Joo  ;  Hak Sung Lee  ;  In-Sik Chung  ;  Yun-Jung Yoo  ;  D Scott Merrell  ;  Jeong-Heon Cha 
Citation
 JOURNAL OF ANTIBIOTICS, Vol.62(1) : 43-50, 2009 
Journal Title
 JOURNAL OF ANTIBIOTICS 
ISSN
 0021-8820 
Issue Date
2009
MeSH
Alleles ; Bacterial Proteins/genetics* ; Drug Resistance, Bacterial/genetics* ; Helicobacter pylori/drug effects* ; Helicobacter pylori/genetics* ; Metronidazole/pharmacology* ; Microbial Sensitivity Tests ; Nitroreductases/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Transformation, Bacterial/drug effects ; Transformation, Bacterial/genetics
Keywords
antibiotic resistance ; FrxA ; genetics ; Helicobacter pylori ; metronidazole ; RdxA
Abstract
Resistance to metronidazole (MTZ) in Helicobacter pylori is associated with mutations in rdxA, encoding an oxygen-insensitive NADPH nitroreductase, and mutations in frxA, encoding a NAD(P)H-flavin oxidoreductase. Despite this association, the strict correlation of MTZ resistance with mutations in rdxA or frxA is still controversial. In this study, rdxA allelic replacement was used to distinguish resistance-associated nucleotide mutations from the natural genetic diversity of H. pylori. Replacement with truncated rdxA resulted in MTZ resistance, whereas replacement with missense-mutated rdxA from resistant clinical isolates failed to yield MTZ resistance. Thus, although truncation of rdxA confers MTZ resistance in G27 H. pylori, MTZ resistance found in other clinical isolates is not due to the identified amino-acid substitutions. Three of our MTZ-resistant clinical isolates expressed functional rdxA and two of these also encoded full-length frxA. Therefore, MTZ resistance can arise in H. pylori possessing functional rdxA, suggesting that other factors are involved in MTZ resistance.
Full Text
http://www.nature.com/ja/journal/v62/n1/full/ja20086a.html
DOI
10.1038/ja.2008.6
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, So Young(김소영)
Yoo, Yun Jung(유윤정) ORCID logo https://orcid.org/0000-0002-0045-9597
Joo, Young Min(주영민)
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103439
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