Samarawickrema, N.A.Brown, D.M.Upcroft, J.A.Thammapalerd, N.Uproft, P.2014-10-292014-10-291997The Journal of Antimicrobial Chemotherapy. 1997; 40: pp.833-8400305-7453 (Print)1460-2091 (Electronic)http://repository.kln.ac.lk/handle/123456789/1304Indexed in MEDLINEMetronidazole 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.Drug ResistanceEntamoeba histolyticaEntamoeba histolytica-drug effectsEntamoeba histolytica-enzymologyKetone Oxidoreductases-metabolismMetronidazoleMetronidazole-pharmacologySuperoxide Dismutase-metabolismComparative StudyArticleBiochemistry