Fertilization and zygote development are obligate features of the malaria p
arasite life cycle and occur during parasite transmission to mosquitoes. Th
e surface protein PFS48/45 is expressed by male and female gametes of Plasm
odium falciparum and PFS48/45 antibodies prevent zygote development and tra
nsmission. Here, gene disruption was used to show that Pfs48/45 and the ort
holog Pbs48/45 from a rodent malaria parasite P. berghei play a conserved a
nd important role in fertilization. p48/45(-) parasites had a reduced capac
ity to produce oocysts in mosquitoes due to greatly reduced zygote formatio
n. Unexpectedly, only male gamete fertility of p48/45(-) parasites was affe
cted, failing to penetrate otherwise fertile female gametes. P48/45 is show
n to be a surface protein of malaria parasites with a demonstrable role in
fertilization.