Publication: Involvement of superoxide dismutase and pyruvate:ferredoxin oxidoreductase in mechanisms of metronidazole resistance in Entamoeba histolytica
7
Issued Date
1997-12-01
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ISSN
03057453
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2-s2.0-0031465651
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Antimicrobial Chemotherapy. Vol.40, No.6 (1997), 833-840
Suggested Citation
Nirma A. Samarawickrema, David M. Brown, Jacqueline A. Upcroft, Nitaya Thammapalerd, Peter Upcroft Involvement of superoxide dismutase and pyruvate:ferredoxin oxidoreductase in mechanisms of metronidazole resistance in Entamoeba histolytica. Journal of Antimicrobial Chemotherapy. Vol.40, No.6 (1997), 833-840. doi:10.1093/jac/40.6.833 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/18056
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Title
Involvement of superoxide dismutase and pyruvate:ferredoxin oxidoreductase in mechanisms of metronidazole resistance in Entamoeba histolytica
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Abstract
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 μM). 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, α-ketobutyrate, α-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.