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Title: | Superoxide dismutase and pyruvate ferrodoxin oxidoreductase involvement in mechanisms of metronidazole resistance in Entamoeba histolytica |
Authors: | Samarawickrema, N.A. Brown, D.M. Upcroft, J.A. Thammapalerd, N. Uproft, P. |
Keywords: | Drug Resistance Entamoeba histolytica Entamoeba histolytica-drug effects Entamoeba histolytica-enzymology Ketone Oxidoreductases-metabolism Metronidazole Metronidazole-pharmacology Superoxide Dismutase-metabolism Comparative Study |
Issue Date: | 1997 |
Publisher: | Oxford University Press |
Citation: | The Journal of Antimicrobial Chemotherapy. 1997; 40: pp.833-840 |
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 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. |
Description: | Indexed in MEDLINE |
URI: | http://repository.kln.ac.lk/handle/123456789/1304 |
ISSN: | 0305-7453 (Print) 1460-2091 (Electronic) |
Appears in Collections: | Journal/Magazine Articles |
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