Role of superoxide dismutase in survival of Leishmania within the macrophage

Abstract

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.

IFN-β Impairs Superoxide-Dependent Parasite Killing in Human Macrophages: Evidence for a Deleterious Role of SOD1 in Cutaneous Leishmaniasis

“…Moreover, the superior effect of DETC, as compared with SOD1 siRNA, might be partially mediated through inhibition of other host (mitochondrial SOD2 and extracellular SOD3) or even Leishmania SOD isoforms. A role for parasite SOD in intramacrophage survival has been previously described in L. tropica (27) and L. chagasi (28). Interestingly, treatment of infected human macrophages with purified SOD1 in vitro led to strongly increased parasite burden and the appearance of large parasitophorous vacuoles (R. Khouri and J.…”

Extracellular Superoxide Dismutase in Insects

“…Production of ROS is part of this response, as evidenced for D. melanogaster (7)(8)(9), and the detoxification of ROS is known to be part of virulence mechanisms. SODs, for instance, are used as immune-suppressive toxins by a large number of pathogens, including eukaryotic protozoan parasites (21)(22)(23)(24)(25)(26).…”

“…This is quite surprising as a well known virulence strategy employed by numerous bacterial and fungal pathogens, including pathogens of insects as well as protozoan parasites, is the detoxification of reactive species by antioxidant enzymes, mainly superoxide dismutases (SODs) (21)(22)(23)(24)(25)(26). SODs are one of the most important cellular enzymatic defenses against the detrimental ROS generated by the aerobic metabolism.…”

Monitoring of intracellular nitric oxide in leishmaniasis: Its applicability in patients with visceral leishmaniasis

“…In Leishmania parasites, their antioxidant defenses are relatively compromised owing to the absence of catalase and classical selenium-dependent glutathione peroxidases (9), thus making them overly reliant upon a relatively less efficient, unique trypanothione dependent antioxidant system (10,11) along with two iron containing superoxide dismutases, which only marginally protect them from free radical mediated damage (12,13). Exploiting the impaired antioxidant capacity of Leishmania parasites, triggering of oxidative stress (reactive oxygen and nitrogen species) seems a logical chemotherapeutic modality.…”