Identification of genes required for Plasmodium gametocyte-to-sporozoite development in the mosquito vector

• Published in: Cell host & microbe Vol. 31; no. 9; pp. 1539 - 1551.e6
• Main Authors: Ukegbu, Chiamaka Valerie, Gomes, Ana Rita, Giorgalli, Maria, Campos, Melina, Bailey, Alexander J., Besson, Tanguy Rene Balthazar, Billker, Oliver, Vlachou, Dina, Christophides, George K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 13.09.2023
• Subjects: crystalloid; gametocyte expression; host-parasite interactions; Life Sciences; malaria transmission; oocyst; ookinete gliding motility; ookinete vesicle trafficking; salivary gland invasion; signature-tagged mutagenesis; sporozoite infectivity; gametocyte expression; sporozoite infectivity; salivary gland invasion; oocyst; malaria transmission; signature-tagged mutagenesis; ookinete gliding motility; crystalloid; host-parasite interactions; ookinete vesicle trafficking
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2023.08.010

Malaria remains one of the most devastating infectious diseases. Reverse genetic screens offer a powerful approach to identify genes and molecular processes governing malaria parasite biology. However, the complex regulation of gene expression and genotype-phenotype associations in the mosquito vector, along with sexual reproduction, have hindered the development of screens in this critical part of the parasite life cycle. To address this, we developed a genetic approach in the rodent parasite Plasmodium berghei that, in combination with barcode sequencing, circumvents the fertilization roadblock and enables screening for gametocyte-expressed genes required for parasite infection of the mosquito Anopheles coluzzii. Our results confirm previous findings, validating our approach for scaling up, and identify genes necessary for mosquito midgut infection, oocyst development, and salivary gland infection. These findings can aid efforts to study malaria transmission biology and to develop interventions for controlling disease transmission. [Display omitted] •Reverse genetic screen reveals Plasmodium genes required during mosquito infection•Ookinete STONES and ROVER are required for motility and mosquito midgut invasion•Crystalloid CRONE and CRYSP are essential for sporogony and sporozoite development•Ookinete motility and crystalloids are candidate targets to block malaria transmission Malaria remains a devastating disease, and new concepts are needed to block transmission between people. Ukegbu et al. present a genetic approach that uncovers genes and processes required for the malaria parasite’s developmental transition through the mosquito vector, such as motility and production of sporozoites that infect humans.