Reverse genetic screen identifies malaria parasite genes required for gametocyte-to-sporozoite development in its mosquito host
Reverse genetic screen identifies malaria parasite genes required for gametocyte-to-sporozoite development in its mosquito host
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DOI：
10.1101/2023.03.14.532540
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
C. V. Ukegbu;A. R. Gomes;Maria Giorgalli;M. Campos;Alexander J Bailey;Tanguy Rene Balthazar Besson
中科院分区：
文献类型：
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作者：
C. V. Ukegbu;A. R. Gomes;Maria Giorgalli;M. Campos;Alexander J Bailey;Tanguy Rene Balthazar Besson
疟疾仍然是最具破坏性的传染病之一。反向基因筛查为识别控制疟疾寄生虫生物学的基因和分子过程提供了一种强大的方法。然而，蚊子的有性繁殖和基因表达的复杂调控以及基因-表型关联阻碍了寄生虫生命周期这一关键部分的筛子的发展。我们在啮齿动物寄生虫伯氏疟原虫中设计了一种遗传方法，与条形码测序相结合，使我们能够克服受精障碍，并筛选感染蚊子按蚊寄生虫所需的配子体表达基因。结果证实了之前的发现，验证了我们扩大规模的方法，并确定了运动运动和蚊子中肠感染、子孢子发育、卵囊出口和唾液腺感染所需的新基因。我们的发现有助于研究疟疾传播生物学和开发控制疾病传播的新干预措施。
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, sexual reproduction and complex regulation of gene expression and genotype-phenotype associations in the mosquito have hampered the development of screens in this key part of the parasite lifecycle. We designed a genetic approach in the rodent parasite Plasmodium berghei, which in conjunction with barcode sequencing allowed us to overcome the fertilization roadblock and screen for gametocyte-expressed genes required for parasite infection of the mosquito Anopheles coluzzii. The results confirmed previous findings, validating our approach for scaling up, and identified new genes required for ookinete motility and mosquito midgut infection and for sporozoite development and oocyst egress and salivary gland infection. Our findings can assist efforts to study malaria transmission biology and develop new interventions to control disease transmission.