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Overexpression of superoxide dismutase in Trypanosoma cruzi results in increased sensitivity to the trypanocidal agents gentian violet and benznidazole

Overexpression of superoxide dismutase in Trypanosoma cruzi results in increased sensitivity to the trypanocidal agents gentian violet and benznidazole

Temperton, Nigel J., Wilkinson, Shane R., Meyer, David J. and Kelly, John M. (1998) Overexpression of superoxide dismutase in Trypanosoma cruzi results in increased sensitivity to the trypanocidal agents gentian violet and benznidazole. Molecular and Biochemical Parasitology, 96 (1-2). pp. 167-176. ISSN 0166-6851 (doi:10.1016/S0166-6851(98)00127-3)

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Abstract

The parasitic protozoan Trypanosoma cruzi is exposed to toxic oxygen metabolites which arise from drug metabolism or immune mechanisms, in addition to those produced by endogenous processes. Identification and functional analysis of parasite enzymes which confer protection against oxidative stress is therefore of importance. To investigate the role of T. cruzi superoxide dismutase (SOD) we transfected epimastigotes with an expression vector containing a putative Fe-SOD gene homologue and achieved overexpression of enzyme activity (5–8 fold). Inhibition studies carried out on the partially purified enzyme revealed azide and H2O2 sensitivity and cyanide insensitivity, the profile expected of an Fe-isoform. Phenotypic analysis of transformed parasites showed that they were more susceptible than control cells to growth inhibition by the trypanocidal drug benznidazole and by gentian violet, an agent which can be used to decontaminate blood supplies in endemic areas. These results may reflect an imbalance in the antioxidant defences of the parasite produced as a result of overexpression of Fe-SOD.

Item Type: Article
Uncontrolled Keywords: Trypanosoma cruzi, transfection, superoxide dismutase, overexpression
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology
R Medicine > RC Internal medicine
Faculty / Department / Research Group: Faculty of Engineering & Science > Medway School of Pharmacy
Related URLs:
Last Modified: 16 Jul 2012 14:07
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/8571

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