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Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host

Konstantinos Koussis1,2,3, Evi Goulielmaki1, Anna Chalari1,4

  • 1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece.

Plos One
|January 21, 2017
PubMed

Insights

Site-2 proteases (S2P) in Plasmodium parasites are crucial for parasite growth and virulence during malaria infection. However, their absence does not impede parasite development in mosquito and mammalian hosts.

Area of Science:

  • Molecular biology
  • Parasitology
  • Biochemistry

Background:

  • Site-2 proteases (S2P) are metalloproteases involved in regulated intramembrane proteolysis (RIP).
  • RIP activates transcription factors, regulating cellular responses like sterol regulation and Notch signaling.
  • Plasmodium parasites utilize regulated proteolysis for essential life cycle pathways.

Purpose of the Study:

  • To investigate the role of Plasmodium-encoded S2P (PbS2P) in malaria parasite development and virulence.
  • To determine the expression and localization of PbS2P throughout the Plasmodium life cycle.

Main Methods:

  • Murine malaria model for in vivo studies.
  • Reverse genetics for PbS2P gene ablation.
  • Endogenous gene tagging for protein localization studies.

Main Results:

  • PbS2P is expressed in all Plasmodium development stages and localizes near the nucleus in invasive stages.
  • PbS2P ablation significantly reduces parasite growth rates and virulence in liver and blood stages.
  • Parasite development in mosquito and mammalian hosts is unaffected by PbS2P absence under physiological conditions.

Conclusions:

  • PbS2P plays a significant role in Plasmodium parasite growth and virulence.
  • PbS2P function appears dispensable or redundant in certain host environments, suggesting alternative pathways.
  • Further research is needed to elucidate the precise roles and potential redundancy of PbS2P in the malaria parasite.

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