The Malaria Research and Reference Reagent Resource (MR4) Center--creating African opportunities.

The Malaria Research and Reference Reagent Resource Center (MR4) is a program to support the international malaria research community. The primary goal is to improve access to well-characterized quality-controlled parasite, host and vector reagents for standardization of assays and other general research purposes. MR4 is open to all scientists worldwide, however many of its inaugural activities will have a focus in Africa, where the concept for the MR4 was born. Reagents are donated to the MR4 Center by malaria researchers and their institutions for distribution to other investigators special arrangements are also possible for developing reagents in-house, or for coordinating reagents for multi-site studies. In addition to providing reagents, the MR4 also aims to promotoe technology transfer and to foster scientific exchange between new and established malaria researchers. This will be done via workshops, training programs, and dissemination of information (electronic and hard copy). Suggestions for reagents, information resources, or training opportunities are welcome from the research community to make this a responsive, service-oriented program.

Oxidant defense enzymes of Plasmodium falciparum.

We have measured and characterized three oxidant defense enzymes in early and late intraerythrocytic stages of the human malarial parasite, Plasmodium falciparum. Isolated early intraerythrocytic stages contain catalase (24.1 mumol min-1 (mg protein)-1) and superoxide dismutase (SOD; 6.3 units (mg protein)-1) but little or no glutathione peroxidase (GPX; less than 2 mumol min-1 (mg protein)-1). Isolated late intraerythrocytic stages of P. falciparum contain slightly less catalase (17.0 mumol min-1 (mg protein)-1) but significantly more GPX (7.7 mumol min-1 (mg protein)-1) and SOD (25.1 units (mg protein)-1). P. falciparum, like P. berghei, probably acquires most of its SOD from its host, since parasite-associated SOD is predominantly cyanide-sensitive, and has the same pI as host SOD. Unlike P. berghei, however, late stages of P. falciparum contain an additional SOD isozyme which is not cyanide-sensitive and may represent an endogenous enzyme. Parasites grown in red cells that have been partially depleted of SOD are more sensitive to exogenously generated superoxide, suggesting some dependence of the parasite on host SOD.

Superoxide dismutase and catalase in the murine malaria, Plasmodium berghei: content and subcellular distribution.

Plasmodium berghei, a murine malaria, lacks endogenous superoxide dismutase (SOD). Instead it appears to take up and concentrate SOD from its host cell, the erythrocyte. We now demonstrate that the adopted host enzyme is localized in granules which are probably lysosomes. In addition, isolated P. berghei parasites contain only low levels of catalase, probably as a result of contamination of the preparation with host cell material. Thus, the cytosol of this organism appears to be deficient in enzymes which protect against damage by activated oxygen.

An iron-containing superoxide dismutase in Tritrichomonas foetus.

Dialysed extracts of Tritrichomonas foetus were found to have superoxide dismutase at substantially higher levels than those found in trypanosomatids and mouse red blood cells. The activity was sensitive to inhibition by H2O2 but not by cyanide, suggesting that this organism has iron-containing superoxide dismutase(s). Three isozymes were seen by isoelectric focusing which appeared to be sensitive to inhibition by H2O2.

Malaria parasites adopt host cell superoxide dismutase.

Aerobic organisms depend on superoxide dismutase to suppress the formation of dangerous species of activated oxygen. Intraerythrocytic stages of the malaria parasite exist within a highly aerobic environment and cause the generation of increased amounts of activated oxygen. Plasmodium berghei in mice was found to derive a substantial amount of superoxide dismutase activity from the host cell cytoplasm. Plasmodia isolated from mouse red cells contained mouse superoxide dismutase, whereas rat-derived parasites contained the rat enzyme. This is believed to be the first example of the acquisition of a host cell enzyme by an intracellular parasite.