Shalini Agarwal
International Centre for Genetic Engineering and Biotechnology, India
Posters-Accepted Abstracts: Clin Microbiol
The release of intra erythrocytic parasites is a fundamental step during blood-stage propagation and transmission of the malaria parasite from the human to the mosquito. Although considerable advances have been made in our understanding of the unique exit mechanisms, the signal that triggers the egress of these different intra erythrocytic stages are not known. Herein, we demonstrate that abscisic acid (ABA) a phyto-hormone that is produced in blood stage parasites plays a critical role in regulation of Ca2+dependent egress of both invasive merozoites and activated gametocytes. Extracts of Plasmodium falciparum analyzed by LC-MS/MS at different time points during the blood stage life cycle revealed a marked spike in ABA levels in late schizonts. Use of herbicide fluridone (FLU), an inhibitor of ABA biosynthetic pathway, reduced the levels of ABA and blocked egress of merozoites as well as of activated gametocytes. Further, addition of exogenous ABA triggered intracellular Ca2+ release in late stage schizonts and also rescued egress of FLU-treated merozoites and gametocytes from the host erythrocyte P. falciparum perforin like proteins PfPLP1 and PfPLP2, which were previously shown to mediate host cell membrane permeabilization during egress of both merozoites and gametocytes, respectively, did not localize to the erythrocyte membrane in FLU-treated infected erythrocytes. These results indicate that ABA synthesis in malaria parasites is a critical step for egress of both merozoites and activated gametocytes. The ABA biosynthesis pathway, which is found in plants and absent in mammalian cells can be explored to identify target to limit blood stage parasite growth and transmission of malaria parasites.
Email: shalini.hcu@gmail.com