Plasmodium falciparum sexual differentiation in malaria patients is associated with host factors and GDV1-dependent genes

Miho Usui*, Surendra K. Prajapati, Ruth Ayanful-Torgby, Festus K. Acquah, Elizabeth Cudjoe, Courage Kakaney, Jones A. Amponsah, Evans K. Obboh, Deepti K. Reddy, Michelle C. Barbeau, Lacy M. Simons, Beata Czesny, Sorana Raiciulescu, Cara Olsen, Benjamin K. Abuaku, Linda E. Amoah, Kim C. Williamson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Plasmodium sexual differentiation is required for malaria transmission, yet much remains unknown about its regulation. Here, we quantify early gametocyte-committed ring (gc-ring) stage, P. falciparum parasites in 260 uncomplicated malaria patient blood samples 10 days before maturation to transmissible stage V gametocytes using a gametocyte conversion assay (GCA). Seventy six percent of the samples have gc-rings, but the ratio of gametocyte to asexual-committed rings (GCR) varies widely (0–78%). GCR correlates positively with parasitemia and is negatively influenced by fever, not hematocrit, age or leukocyte counts. Higher expression levels of GDV1-dependent genes, ap2-g, msrp1 and gexp5, as well as a gdv1 allele encoding H217 are associated with high GCR, while high plasma lysophosphatidylcholine levels are associated with low GCR in the second study year. The results provide a view of sexual differentiation in the field and suggest key regulatory roles for clinical factors and gdv1 in gametocytogenesis in vivo.

Original languageEnglish
Article number2140
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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