1887

Abstract

Mutations in the NAD(P)H flavin oxidoreductase gene () are thought to contribute to the development of metronidazole resistance in . To test this further, 44 sequences in 18 patient isolate sets of were examined including a unique collection comprising separated Mtz-sensitive (Mtz) and Mtz-resistant (Mtz) subpopulations pre-treatment and matched Mtz strains post-treatment. Sequences of contained frameshift mutations that led to premature protein truncation in at least one strain from most (17/18) patient sets. These mutations were present in all strains, irrespective of Mtz resistotype in 13/18 patients. Frameshift due to a single adenine deletion at nucleotide 53 was the most common mutation and was present in isolates from 11/18 patients. A novel real-time (LightCycler) PCR-based probe hybridization melting-point assay applied to a further 119 isolates confirmed that the frameshift-53 mutation occurred frequently, in 20 % of isolates, and could be present in Mtz as well as Mtz strains (42 % vs 58 %). This study demonstrates that frameshift mutations occur in Mtz strains as well as in Mtz strains, and are thus unlikely to cause Mtz resistance.

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2004-02-01
2019-11-19
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