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Analysis of sex-specific lipid metabolism of Plasmodium falciparum points to the importance of sphingomyelin for gametocytogenesis

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dc.contributor.authorRidgway, M.C.
dc.contributor.authorCihalova, D.
dc.contributor.authorBrown, S.H.J.
dc.contributor.authorTran, P.
dc.contributor.authorMitchell, T.W.
dc.contributor.authorMaier, A.G.
dc.date.issued2022
dc.description.abstractMale and female Plasmodium falciparum gametocytes are the parasite lifecycle stage responsible for transmission of malaria from the human host to the mosquito vector. Not only are gametocytes able to survive in radically different host environments, but they are also precursors for male and female gametes that reproduce sexually soon after ingestion by the mosquito. Here, we investigate the sex-specific lipid metabolism of gametocytes within their host red blood cell. Comparison of the male and female lipidome identifies cholesteryl esters and dihydrosphingomyelin enrichment in female gametocytes. Chemical inhibition of each of these lipid types in mature gametocytes suggests dihydrosphingomyelin synthesis but not cholesteryl ester synthesis is important for gametocyte viability. Genetic disruption of each of the two sphingomyelin synthase genes points towards sphingomyelin synthesis contributing to gametocytogenesis. This study shows that gametocytes are distinct from asexual stages, and that the lipid composition is also vastly different between male and female gametocytes, reflecting the different cellular roles these stages play. Taken together, our results highlight the sex-specific nature of gametocyte lipid metabolism, which has the potential to be targeted to block malaria transmission.
dc.description.statementofresponsibilityMelanie C. Ridgway, Daniela Cihalova, Simon H. J. Brown, Phuong Tran, Todd W. Mitchell, and Alexander G. Maier
dc.identifier.citationJournal of Cell Science, 2022; 135(5):jcs259592-1-jcs259592-13
dc.identifier.doi10.1242/jcs.259592
dc.identifier.issn0021-9533
dc.identifier.issn1477-9137
dc.identifier.orcidRidgway, M.C. [0000-0002-6763-2366]
dc.identifier.urihttps://hdl.handle.net/2440/149193
dc.language.isoen
dc.publisherThe Company of Biologists
dc.relation.granthttp://purl.org/au-research/grants/arc/DP180103212
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1182369
dc.rights© 2022. Published by The Company of Biologists Ltd.
dc.source.urihttps://doi.org/10.1242/jcs.259592
dc.subjectGametocytes; Lipidome; Malaria; Plasmodium falciparum; Sphingomyelin; transmission
dc.subject.meshAnimals
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshLife Cycle Stages
dc.subject.meshLipid Metabolism
dc.subject.meshMalaria, Falciparum
dc.subject.meshMale
dc.subject.meshMosquito Vectors
dc.subject.meshPlasmodium falciparum
dc.subject.meshSphingomyelins
dc.titleAnalysis of sex-specific lipid metabolism of Plasmodium falciparum points to the importance of sphingomyelin for gametocytogenesis
dc.typeJournal article
pubs.publication-statusPublished

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