Journal of Antimicrobial Chemotherapy, Vol 40, 833-840, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
NA Samarawickrema, DM Brown, JA Upcroft, N Thammapalerd and P Upcroft
Metronidazole resistance has been induced in an axenic strain of Entamoeba
histolytica (HTH-56:MUTM) following continuous exposure to steadily
increasing drug concentrations. The drug-resistant line is routinely
maintained in normally lethal levels of metronidazole (10 microM).
Resistance to this concentration of drug was developed over 177 days.
Decreased pyruvate:ferredoxin oxidoreductase (PFOR) activity in anaerobic
organisms is one mechanism of metronidazole resistance but in entamoeba,
PFOR activity was not decreased in metronidazole- resistant parasites as
determined by immunofluorescent assays and immunoblotting studies.
2-Oxoacid oxidoreductase activity, which appeared to be due to a single
enzyme, PFOR, was evident with pyruvate as well as the alternative
substrates, alpha-ketobutyrate, alpha- ketoglutarate and oxaloacetate. A
marked increase in superoxide dismutase (SOD) activity was detected in
metronidazole-resistant E. histolytica. Increased SOD activity has not
previously been documented as a mechanism of drug resistance although SOD
has been associated with a range of stress situations in other organisms.
ORIGINAL ARTICLES
Involvement of superoxide dismutase and pyruvate:ferredoxin oxidoreductase in mechanisms of metronidazole resistance in Entamoeba histolytica
Queensland Institute of Medical Research, The Bancroft Centre, Brisbane, Australia.
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