AUTHOR=Liu Fei , Liu Qingyang , Yu Chunyun , Zhao Yan , Wu Yudi , Min Hui , Qiu Yue , Jin Ying , Miao Jun , Cui Liwang , Cao Yaming 

TITLE=An MFS-Domain Protein Pb115 Plays a Critical Role in Gamete Fertilization of the Malaria Parasite Plasmodium berghei

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02193

DOI=10.3389/fmicb.2019.02193

ISSN=1664-302X

ABSTRACT=<p>Sexual reproduction is an essential process in the <italic>Plasmodium</italic> 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 <italic>Plasmodium berghei</italic> 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 <italic>P. berghei</italic>, genetic deletion of <italic>Pb115</italic> (Δ<italic>pb115</italic>) did not affect asexual multiplication, nor did it affect gametocyte development or exflagellation of the male gametocytes. However, mosquitoes fed on Δ<italic>pb115</italic>-infected mice showed 74% reduction in the prevalence of infection and 96.5% reduction in oocyst density compared to those fed on wild-type <italic>P. berghei</italic>-infected mice. The Δ<italic>pb115</italic> 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 Δ<italic>pbs48/45</italic> line and the female-defective Δ<italic>pfs47</italic> line further indicated that the fertilization defects of the Δ<italic>pb115</italic> 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. <italic>In vivo</italic> 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 <italic>Plasmodium</italic> and demonstrated transmission-blocking potential of this antigen.</p>