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

Nat Commun. 2019 May 13;10(1):2140. doi: 10.1038/s41467-019-10172-6.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Age Factors
  • Child
  • Child, Preschool
  • Female
  • Gametogenesis / physiology
  • Genes, Protozoan / physiology
  • Ghana
  • Host-Parasite Interactions / physiology*
  • Humans
  • Lysophosphatidylcholines / blood
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / parasitology*
  • Male
  • Parasitemia / parasitology
  • Plasmodium falciparum / isolation & purification
  • Plasmodium falciparum / physiology*
  • Protozoan Proteins / physiology*
  • Sex Differentiation / physiology*

Substances

  • Lysophosphatidylcholines
  • Protozoan Proteins