Journal of Antimicrobial Chemotherapy, Vol 39, 347-353, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
MA Smith and DI Edwards
Failure of triple-therapy regimes to eradicate Helicobacter pylori from the
stomach is thought to be due to the occurrence of a metronidazole-
resistant bacterial population. Exposure of metronidazole-resistant (MtzR)
strains of H. pylori to an anaerobic environment causes the activation of
metronidazole and the loss of resistance. Using metronidazole-sensitive
(MtzS) clinical isolates, we selected mutants conferring resistance to
metronidazole, which were used to investigate the effect of bacterial cell
density upon the activation of metronidazole. The addition of
metronidazole, at a final concentration of 10 mg/L, to MtzR cultures of a
bacterial cell density >1 x 10(6) cfu/mL, caused a loss in viability. No
loss in viability, however, occurred upon addition of metronidazole to MtzR
cultures of a cell density of <1 x 10(6) cfu/mL. MtzS cultures lost
viability irrespective of the initial cell density, indicating that oxygen
scavenging at the site of metronidazole reduction may occur in these
cultures. The ability of MtzS wild types, MtzR isogenic mutants and MtzR
wild types to scavenge oxygen from the intracellular environment was
investigated. H. pylori cultures contained NADH and NADPH oxidase activity.
NADPH oxidase activity was always more than double the NADH oxidase
activity. MtzR mutants possessed approximately one-third the NADH oxidase
activity found in their respective MtzS parent wild types. MtzR wild types
possessed a low NADH oxidase level similar to that found in the MtzR
mutants. We propose that metronidazole resistance may be mediated through
an inability of MtzR strains to remove oxygen from the site of
metronidazole reduction, thereby preventing metronidazole activation.
JOURNAL ARTICLE
Oxygen scavenging, NADH oxidase and metronidazole resistance in Helicobacter pylori
Chemotherapy Research Unit, University of East London, Stratford Campus, UK.
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