Aedes aegypti SGS1 is critical for Plasmodium gallinaceum infection of both the mosquito midgut and salivary glands.

Aedes aegypti SGS1 is critical for Plasmodium gallinaceum infection of both the mosquito midgut and salivary glands.
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DOI:
10.1186/s12936-020-03537-6
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发表时间:
2021-01-06
期刊:
影响因子:
3
通讯作者:
Adelman ZN
Adelman ZN
中科院分区:
医学3区
文献类型:
--
作者:
Kojin BB;Martin-Martin I;Araújo HRC;Bonilla B;Molina-Cruz A;Calvo E;Capurro ML;Adelman ZN

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疟原虫子孢子入侵蚊子唾液腺是决定疟疾传播成功与否的关键一步,对唾液腺入侵分子的详细了解可用于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鸡疟原虫子孢子对埃及伊蚊唾液腺的入侵,但该蛋白在子孢子入侵和疟原虫生命周期的其他阶段中的具体作用仍不清楚。 RNA 干扰和 CRISPR/Cas9 用于评估埃及伊蚊 SGS1 在鸡 P. 生命周期中的作用。 SGS1 的敲低和敲除破坏了子孢子对唾液腺的侵袭。有趣的是,缺乏 SGS1 的蚊子也表现出较少的卵囊。蛋白质组学分析证实,SGS1 基因敲除蚊子的唾液腺中 SGS1 被消除,并揭示对照蚊子的唾液腺中不存在该蛋白质的 C 末端。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 促进鸡疟原虫侵入埃及伊蚊唾液腺,但不是必需的,并且具有促进蚊子中肠寄生虫发育的双重作用。因此,SGS1 可能成为减少蚊子媒介传播疟疾的策略的一部分,例如在转基因蚊子中阻止其与寄生虫的相互作用。
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.
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