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 and Kim C. Williamson
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Miho Usui: Uniformed Services University of the Health Sciences
Surendra K. Prajapati: Uniformed Services University of the Health Sciences
Ruth Ayanful-Torgby: University of Ghana
Festus K. Acquah: University of Ghana
Elizabeth Cudjoe: University of Ghana
Courage Kakaney: University of Ghana
Jones A. Amponsah: University of Ghana
Evans K. Obboh: University of Cape Coast
Deepti K. Reddy: Uniformed Services University of the Health Sciences
Michelle C. Barbeau: Uniformed Services University of the Health Sciences
Lacy M. Simons: Loyola University Chicago
Beata Czesny: Loyola University Chicago
Sorana Raiciulescu: Uniformed Services University of the Health Sciences
Cara Olsen: Uniformed Services University of the Health Sciences
Benjamin K. Abuaku: University of Ghana
Linda E. Amoah: University of Ghana
Kim C. Williamson: Uniformed Services University of the Health Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10172-6

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