Affiliations 

  • 1 Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
  • 2 Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands
  • 3 Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, United States
  • 4 Microbiology and Immunology Department, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States
  • 5 Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. S.M.Khan@lumc.nl
Sci Rep, 2018 10 08;8(1):14902.
PMID: 30297725 DOI: 10.1038/s41598-018-33236-x

Abstract

Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important for gamete fertility in rodent and human malaria parasites and are leading transmission blocking vaccine antigens. Rodent and human parasites encode a paralog of P230, called P230p. While P230 is expressed in male and female parasites, P230p is expressed only in male gametocytes and gametes. In rodent malaria parasites this protein is dispensable throughout the complete life-cycle; however, its function in P. falciparum is unknown. Using CRISPR/Cas9 methodology we disrupted the gene encoding Pfp230p resulting in P. falciparum mutants (PfΔp230p) lacking P230p expression. The PfΔp230p mutants produced normal numbers of male and female gametocytes, which retained expression of P48/45 and P230. Upon activation male PfΔp230p gametocytes undergo exflagellation and form male gametes. However, male gametes are unable to attach to red blood cells resulting in the absence of characteristic exflagellation centres in vitro. In the absence of P230p, zygote formation as well as oocyst and sporozoite development were strongly reduced (>98%) in mosquitoes. These observations demonstrate that P230p, like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and warrants further investigation as a potential transmission blocking vaccine candidate.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.