Chandana, M and Anand, A and Ghosh, S and Das, R and Beura, S and Jena, S and Suryawanshi, AR and Padmanaban, G and Nagaraj, VA (2022) Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice. In: Nature Communications, 13 (1).
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Abstract
Heme-biosynthetic pathway of malaria parasite is dispensable for asexual stages, but essential for mosquito and liver stages. Despite having backup mechanisms to acquire hemoglobin-heme, pathway intermediates and/or enzymes from the host, asexual parasites express heme pathway enzymes and synthesize heme. Here we show heme synthesized in asexual stages promotes cerebral pathogenesis by enhancing hemozoin formation. Hemozoin is a parasite molecule associated with inflammation, aberrant host-immune responses, disease severity and cerebral pathogenesis. The heme pathway knockout parasites synthesize less hemozoin, and mice infected with knockout parasites are protected from cerebral malaria and death due to anemia is delayed. Biosynthetic heme regulates food vacuole integrity and the food vacuoles from knockout parasites are compromised in pH, lipid unsaturation and proteins, essential for hemozoin formation. Targeting parasite heme synthesis by griseofulvin—a FDA-approved antifungal drug, prevents cerebral malaria in mice and provides an adjunct therapeutic option for cerebral and severe malaria.
| Item Type: | Journal Article |
|---|---|
| Publication: | Nature Communications |
| Publisher: | Nature Research |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | anemia; disease severity; malaria; mosquito; parasite, griseofulvin; heme; hemoglobin, animal; cerebral malaria; metabolism; mouse; parasite, Animals; Griseofulvin; Heme; Hemoglobins; Malaria, Cerebral; Mice; Parasites |
| Department/Centre: | Division of Biological Sciences > Biochemistry |
| Date Deposited: | 17 Sep 2022 03:06 |
| Last Modified: | 09 Aug 2024 10:39 |
| URI: | http://eprints.iisc.ac.in/id/eprint/76570 |
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