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Phenotypic Analysis of Rodent Malaria Parasite Asexual and Sexual Blood Stages and Mosquito Stages
Published on: May 30, 2019
The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites
Mariana De Niz1,2, Ann-Katrin Ullrich3, Arlett Heiber3
1Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.
Abstract:
Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence.
Insights
Malaria parasite sequestration in organs is key to disease. Researchers found conserved proteins in rodent malaria models, validating their use for studying human malaria virulence.
Area of Science:
- Malariology
- Parasitology
- Molecular Biology
Background:
- Sequestration of Plasmodium falciparum-infected red blood cells in organs contributes to malaria pathogenicity.
- Understanding conserved mechanisms of sequestration is crucial for developing effective treatments.
Purpose of the Study:
- To identify Plasmodium berghei orthologues of Plasmodium falciparum sequestration factors SBP1 and MAHRP1.
- To investigate the role of these conserved proteins in parasite sequestration and virulence in a rodent malaria model.
Main Methods:
- Gene identification and knockout of SBP1 and MAHRP1 in P. berghei.
- Assessment of infected red blood cell binding to CD36.
- Evaluation of parasite sequestration and virulence in infected mice.
Main Results:
- P. berghei parasites lacking SBP1 or MAHRP1a showed impaired binding to CD36.
- These mutant parasites exhibited reduced sequestration and virulence in mice.
- Complementation with P. falciparum SBP1 and MAHRP1 restored sequestration and virulence.
Conclusions:
- The study demonstrates evolutionary conservation of sequestration machinery between P. falciparum and P. berghei.
- The P. berghei rodent model is validated as a suitable tool for malaria virulence research.
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