Role of superoxide dismutase in survival of Leishmania within the macrophage.
Intracellular parasitic protozoans of the genus Leishmania depend for their survival on the elaboration of enzymic and other mechanisms for evading toxic free-radical damage inflicted by their phagocytic macrophage host. One such mechanism may involve superoxide dismutase (SOD), which detoxifies reactive superoxide radicals produced by activated macrophages, but the role of this enzyme in parasite survival has not yet been demonstrated. We have cloned a SOD gene from L. tropica and generated SOD-deficient parasites by expressing the corresponding antisense RNA from an episomal vector. Such parasites have enhanced sensitivity to menadione and hydrogen peroxide in axenic culture, and a markedly reduced survival in mouse macrophages. These results indicate that SOD is a major determinant of intracellular survival of Leishmania.
Ghosh
Sanjay
S
Genetic Engineering laboratory, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700 032, India. sadhya@iicb.res.in
Goswami
Srikanta
S
Adhya
Samit
S
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013482:Superoxide Dismutase / Q000502:physiology*; D015996:Survival Rate
D016877:Oxidants; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase