Department of Entomology and Agrilife Research, Texas A&M University, College Station, TX, USA.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.
Malar J. 2021 Jan 6;20(1):11. doi: 10.1186/s12936-020-03537-6.
The invasion of the mosquito salivary glands by Plasmodium sporozoites is a critical step that defines the success of malaria transmission and a detailed understanding of the molecules responsible for salivary gland invasion could be leveraged towards control of vector-borne pathogens. Antibodies directed against the mosquito salivary gland protein SGS1 have been shown to reduce Plasmodium gallinaceum sporozoite invasion of Aedes aegypti salivary glands, but the specific role of this protein in sporozoite invasion and in other stages of the Plasmodium life cycle remains unknown.
RNA interference and CRISPR/Cas9 were used to evaluate the role of A. aegypti SGS1 in the P. gallinaceum life cycle.
Knockdown and knockout of SGS1 disrupted sporozoite invasion of the salivary gland. Interestingly, mosquitoes lacking SGS1 also displayed fewer oocysts. Proteomic analyses confirmed the abolishment of SGS1 in the salivary gland of SGS1 knockout mosquitoes and revealed that the C-terminus of the protein is absent in the salivary gland of control mosquitoes. In silico analyses indicated that SGS1 contains two potential internal cleavage sites and thus might generate three proteins.
SGS1 facilitates, but is not essential for, invasion of A. aegypti salivary glands by P. gallinaceum and has a dual role as a facilitator of parasite development in the mosquito midgut. SGS1 could, therefore, be part of a strategy to decrease malaria transmission by the mosquito vector, for example in a transgenic mosquito that blocks its interaction with the parasite.
疟原虫孢子侵入蚊子的唾液腺是疟疾传播成功的关键步骤，如果能深入了解导致唾液腺入侵的分子，就可以利用这些知识来控制媒介传播的病原体。针对蚊子唾液腺蛋白 SGS1 的抗体已被证明可以减少恶性疟原虫孢子侵入埃及伊蚊的唾液腺，但该蛋白在孢子入侵和疟原虫生命周期的其他阶段的具体作用仍不清楚。
使用 RNA 干扰和 CRISPR/Cas9 来评估 A. aegypti SGS1 在 P. gallinaceum 生命周期中的作用。
SGS1 的敲低和敲除破坏了唾液腺中孢子的入侵。有趣的是，缺乏 SGS1 的蚊子的卵囊数量也较少。蛋白质组学分析证实了 SGS1 在 SGS1 敲除蚊子的唾液腺中被废除，并表明该蛋白的 C 端在对照蚊子的唾液腺中不存在。计算机分析表明 SGS1 包含两个潜在的内部切割位点，因此可能产生三种蛋白质。
SGS1 促进了 P. gallinaceum 对 A. aegypti 唾液腺的入侵，但不是必需的，并且在蚊子中肠中寄生虫发育的促进中具有双重作用。因此，SGS1 可以成为减少蚊子传播疟疾的策略的一部分，例如在一种阻止其与寄生虫相互作用的转基因蚊子中。
