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

So Yeong Kim, Young Min Joo, Hak Sung Lee, In Sik Chung, Yun Jung Yoo, D. Scott Merrell, Jeong Heon Cha

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalJournal of Antibiotics
Volume62
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

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