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Stearoyl-CoA desaturase regulates membrane biogenesis and hepatic merozoite formation in Plasmodium berghei
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  • Sunil Kumar Narwal,
  • Akancha Mishra,
  • Ankit Ghosh,
  • Hadi Hasan Choudhary,
  • Satish Mishra
Sunil Kumar Narwal
CSIR-Central Drug Research Institute
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Akancha Mishra
CSIR-Central Drug Research Institute
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Ankit Ghosh
CSIR-Central Drug Research Institute
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Hadi Hasan Choudhary
CSIR-Central Drug Research Institute
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Satish Mishra
CSIR-Central Drug Research Institute

Corresponding Author:[email protected]

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Abstract

Plasmodium is an obligate intracellular parasite that requires intense lipid synthesis for membrane biogenesis and survival. One of the principal membrane components is oleic acid, which is required to maintain the membrane’s biophysical properties and fluidity. The malaria parasite Plasmodium can modify fatty acids, and stearoyl-CoA Δ9-desaturase (Scd) is an enzyme that catalyzes the synthesis of oleic acid by desaturation of stearic acid. Scd is dispensable in P. falciparum blood stages; however, its role in mosquito and liver stages remains unknown. We show that P. berghei Scd localizes to the ER in the blood and liver stages. Disruption of Scd in the rodent malaria parasite P. berghei did not affect parasite blood stage propagation, mosquito stage development, or early liver stage development. However, when scd KO sporozoites were inoculated intravenously or by mosquito bite into mice, they failed to initiate blood-stage infection. Immunofluorescence analysis revealed that organelle biogenesis was impaired and merozoite formation was abolished, which normally initiates blood-stage infections. Genetic complementation of the KO parasites restored merozoite formation to a level similar to that of WT parasites. Mice immunized with Scd KO sporozoites confer long-lasting sterile protection against infectious sporozoite challenge. Thus, the Scd KO parasite is an appealing candidate for inducing protective preerythrocytic immunity.
14 Aug 2023Submitted to Molecular Microbiology
16 Aug 2023Assigned to Editor
16 Aug 2023Submission Checks Completed
17 Aug 2023Reviewer(s) Assigned
22 Sep 2023Review(s) Completed, Editorial Evaluation Pending
27 Sep 2023Editorial Decision: Revise Minor