Authors

A Bailey¹; ²; D Vlachou¹; ²; GK Christophides¹; ²;  ¹ Imperial College London, UK;  ² Imperial College London, UK

Discussion

Malaria remains a substantial global health burden. Recent years have seen a significant slowdown in the drop of malaria cases followed by a sharp rise in both cases and deaths in 2020. Inside the mosquito vector, the malaria parasite encounters a significant bottleneck in population size arriving at the sessile oocyst stage, during which many rounds of endomitotic replication leads to a recovery of parasite numbers at the sporozoite stage. The oocyst is therefore an attractive intervention target, but much about its physiology and interaction with the vector remains uncharacterised. Here, we used high throughput RNA-seq to shed light on how Plasmodium falciparum oocysts respond to dynamic nutrient stresses in the mosquito Anopheles gambiae. Analysis of the parasite and mosquito transcriptomes across time has uncovered a parasite developmental trajectory that is remarkably preserved between dramatically different vector mosquito environments; the main outcome of nutrient abundance or stress in the mosquito is to accelerate or slow oocyst development, respectively. Two main developmental transcription programmes are identified in the oocyst, one directing growth and endomitotic replication, and the other orchestrating sporogony, the process of sporozoite production. These programmes appear to be regulated by an array of AP2-domain transcription factors expressed at different stages of oocyst development. These results shed new light on the gene expression networks directing parasite development at this vulnerable life stage and may guide future efforts to better understand and target malaria parasites in the mosquito.