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.

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.