Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites

Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204167119. doi: 10.1073/pnas.2204167119. Epub 2022 Aug 16.

Abstract

Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum, the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission.

Keywords: Plasmodium falciparum; basal complex; malaria; transmission.

MeSH terms

  • Animals
  • Antimalarials / chemistry
  • Drug Design
  • Gametogenesis*
  • Malaria, Falciparum* / parasitology
  • Malaria, Falciparum* / transmission
  • Plasmodium falciparum* / genetics
  • Plasmodium falciparum* / growth & development
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism

Substances

  • Antimalarials
  • Protozoan Proteins