Malaria sporozoites that lack egress cysteine protease 1 get trapped inside the oocyst (shown) in the mosquito midgut.

Malaria sporozoites that lack a certain protease get trapped in their cyst-like breeding ground (the oocyst), as shown by Aly and Matuschewski (page 225). Unable to break free, these captive parasites turn in helpless circles inside the oocyst and their life cycle halts.

Malaria-causing parasites (Plasmodium species) have a complex life cycle that includes several distinct stages of intracellular growth in vertebrate and mosquito hosts. Movement from one stage to the next requires exit from one host cell and entry into another. Invasion of target cells has been shown to require parasite-encoded proteases that, by poorly defined mechanisms, allow the bug to penetrate cell membranes. Parasite exit from target cells has been even less well-studied.Aly and Matuschewski now identify a cysteine protease that is selectively expressed at the late sporozoite stage, just before sporozoite release and entry into the mosquito salivary glands. Elimination of this protease from the parasite caused mature sporozoites to become trapped inside the oocyst, a protective compartment forged from the basal lamina of the mosquito midgut where the sporozoites divide and grow. There they commenced an unusual circular motion, the significance of which is not yet understood.

These data suggest that Plasmodium egress is an active process that requires the protease—dubbed egress cysteine protease 1—to actively break down the oocyst wall, rather than a passive one in which the oocyst simply ruptures once it is filled to capacity.