Fertilization is a novel attacking site for the transmission blocking of malaria parasites

Malaria parasites perform sexual reproduction in mosquitoes where a pair of gametes fertilizes and differentiates into zygotes, and a single zygote produces several thousands of progeny infectious to next vertebrates. Although the parasite fertilization step has been considered as Achilles' heel of parasite life cycle and thus a critical target for blocking malaria transmission in the mosquito, its molecular mechanisms are largely unknown. Previously, we identified that GENERATIVE CELL SPECIFIC 1 (GCS1) is a reproduction factor in angiosperm. Subsequently, it was found that rodent malaria parasite, Plasmodium berghei and green algae, Chlamydomonas reinhardtii possess GCS1 homologues which also play essential roles in gamete interaction. Moreover, intensive database mining revealed that GCS1-like gene homologues exist in the genomes of various organisms. Thus, it appears that GCS1 is an ancient and highly conserved molecule functioning at gamete interaction. In this mini-review, we describe the mechanisms of gametogenesis and fertilization in malaria parasites, comparing with other eukaryotic reproduction, and also speculate GCS1 functions in gamete interaction. We discuss the possibility of whether malaria GCS1 is a novel type of transmission blocking vaccine, by which anti-malaria GCS1 antibody may halt parasite fertilization and subsequent developments in the mosquitoes.