Abstract
Sexual reproduction is an essential process in the Plasmodium life cycle and a vulnerable step for blocking transmission from the human host to mosquitoes. In this study, we characterized the functions of a conserved cell membrane protein P115 in the rodent malaria parasite Plasmodium berghei ANKA. Pb115 was expressed in both asexual stages (schizonts) and sexual stages (gametocytes, gametes, and ookinetes), and was localized on the plasma membrane of gametes and ookinetes. In P. berghei, genetic deletion of Pb115 (Δpb115) did not affect asexual multiplication, nor did it affect gametocyte development or exflagellation of the male gametocytes. However, mosquitoes fed on Δpb115-infected mice showed 74% reduction in the prevalence of infection and 96.5% reduction in oocyst density compared to those fed on wild-type P. berghei-infected mice. The Δpb115 parasites showed significant defects in the interactions between the male and female gametes, and as a result, very few zygotes were formed in ookinete cultures. Cross fertilization with the male-defective Δpbs48/45 line and the female-defective Δpfs47 line further indicated that the fertilization defects of the Δpb115 lines were present in both male and female gametes. We evaluated the transmission-blocking potential of Pb115 by immunization of mice with a recombinant Pb115 fragment. In vivo mosquito feeding assay showed Pb115 immunization conferred modest, but significant transmission reducing activity with 44% reduction in infection prevalence and 39% reduction in oocyst density. Our results described functional characterization of a conserved membrane protein as a fertility factor in Plasmodium and demonstrated transmission-blocking potential of this antigen.
Highlights
Malarial incidence has significantly decreased in recent years due to a range of actions, including the deployment of insecticide-treated nets, indoor residual spraying and artemisinin-based combination therapies (Bhatt et al, 2015)
During the complex life cycle of malaria parasite, sexual stages are obligative for the transmission of the parasite from the human host to the mosquitoes
We identified Pb115, an evolutionarily conserved, putative membrane protein that is expressed in both asexual and sexual stages of the malaria parasites
Summary
Malarial incidence has significantly decreased in recent years due to a range of actions, including the deployment of insecticide-treated nets, indoor residual spraying and artemisinin-based combination therapies (Bhatt et al, 2015). Recent World Health Organization reports showed that the global progress toward malaria elimination has stalled (World Health Organization [WHO], 2018). To achieve global elimination of malaria, an integrated malaria control strategy and novel interventions are needed, which may include measures that interrupt and inhibit disease transmission. During the complex life cycle of malaria parasite, sexual stages are obligative for the transmission of the parasite from the human host to the mosquitoes. Male and female gametocytes formed in the human blood, after ingestion by a female anopheline mosquito, undergo gametogenesis to form gametes, which fuse to form zygotes. Zygotes mature into ookinetes, which penetrate the midgut epithelium to differentiate into oocysts
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