Malaria is among the deadliest infectious diseases, killing in
excess of one million people every year, mostly of African children
under the age of five. Transmission is entirely dependent on the
completion of the life cycle of Plasmodium, the causative agent of
malaria, in its mosquito vector. After ingestion of an infectious
blood meal, Plasmodium gametocytes differentiate into male and
female gametes that fertilize to generate a diploid zygote. After a
round of DNA replication, the tetraploid zygote differentiates into
a motile ookinete. At approximately 24 h after ingestion the
ookinete invades the mosquito midgut and differentiates into
sessile oocysts. Within 7 to 14 days (depending on parasite species),
thousands of sporozoites are released from each oocyst into the
mosquito hemocoel. Sporozoites must successfully invade the
salivary glands to ensure transmission when the infected mosquito
bites and inoculates sporozoites into a new individual [1,2]. The
parasite life cycle in its mosquito host is complex, and dramatic
losses in parasite numbers occur at each stage of Plasmodium
development [2,3]. Ookinete midgut invasion represents the
largest bottleneck in parasite numbers [2,3], as ookinetes must
overcome the effects of the mosquito midgut microbiota and the
innate immune responses in order to successfully transition into an
oocyst [4].