Comparative Biology of Apicomplexa Parasites
Apicomplexa are eukaryotic intracellular parasites of great medical importance. In terms of human public health, the two most significant Apicomplexa are Plasmodium and particularly P. falciparum responsible for severe malaria and Toxoplasma gondii, whose primary infection in pregnant women can lead to serious consequences for the fetus and, in immunocompromised individuals, cyst reactivation can be fatal. Lastly, Theileria is responsible for what is a major scourge for cattle in tropical areas.
The common feature of these three apicomplexan parasites is that activation of the intracellular parasite’s cell cycle results in diseases.
Mechanisms regulating dynamics of parasite multiplication seem to be common and sensitive to the redox equilibrium in the different infected host cells. Thus, many groups including our own have shown that oxidative stress entailed a slow-down in cell cycle progression (e.g. quiescence for P. falciparum, tachyzoite to bradyzoite for Toxoplasma, loss of virulence for T. annulata) linked with the arrest of translation.
Our project aims to characterize the impact of oxidative stress on cell cycle regulation in Apicomplexa.
We hypothesize that understanding how pro-oxidant anti-parasite drugs modify cell cycle regulation could help provide new avenues for the development of appropriate anti-parasite therapeutic interventions.
Because artemisinin resistance poses a major risk to the success of the malaria elimination strategy advocated by WHO, we have chosen to focus on artemisinin induced dormancy in P. falciparum both on laboratory model of cultured parasites and from fields isolates through our collaborations (Pasteur Network, IRD and National Reference Center).