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.
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Acknowledgements
We thank Joong-Chul Lee for the gift of plasmid pILL600, Doug Berg for helpful suggestions and H Gancz and B Carpenter for a critical reading of the paper. This study was supported by the Korea Research Foundation Grant, which was funded by the Korean Government (MOEHRD) (KRF-2006-311-E00083).
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Kim, S., Joo, Y., Lee, H. et al. Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA. J Antibiot 62, 43–50 (2009). https://doi.org/10.1038/ja.2008.6
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DOI: https://doi.org/10.1038/ja.2008.6
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