Identification and characterization of a mosquito-specific eggshell organizing factor in Aedes aegypti mosquitoes
Identification and characterization of a mosquito-specific eggshell organizing factor in Aedes aegypti mosquitoes
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DOI：
10.1371/journal.pbio.3000068
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发表时间：
2019-01-01
期刊：
影响因子：
9.8
通讯作者：
Miesfeld, Roger L.
中科院分区：
文献类型：
--
作者：
Isoe, Jun;Koch, Lauren E.;Miesfeld, Roger L.
蚊子传播的疾病每年在世界各地造成数百万人死亡。控制蚊子种群的一种方法是破坏分子过程或拮抗产生可存活卵所需的新代谢靶点。为此，我们集中精力鉴定完成胚胎发育所需的蛋白质，这些蛋白质是蚊子选择性的，代表了病媒控制的潜在靶标。我们进行了生物信息学分析，以确定推定的蛋白质编码序列，是特定的蚊子基因组。通过将双链RNA（dsRNA）注射到雌性埃及伊蚊中，对40个蚊子特异性基因进行系统性RNA干扰（RNAi）筛选。这种实验方法导致了蛋壳组织因子1（EOF1，AAEL 012336）的鉴定，它在蛋壳的形成和黑化中起着至关重要的作用。由EOF1缺陷型蚊子所产下的卵具有非黑化的易碎蛋壳，并且所有胚胎都不能存活。扫描电子显微镜（SEM）分析表明，外绒毛膜蛋壳结构受到强烈影响EOF1缺陷的蚊子。据我们所知，EOF1是一个潜在的新靶点，用于探索识别和开发蚊子选择性和生物安全的小分子抑制剂。
Mosquito-borne diseases are responsible for several million human deaths annually around the world. One approach to controlling mosquito populations is to disrupt molecular processes or antagonize novel metabolic targets required for the production of viable eggs. To this end, we focused our efforts on identifying proteins required for completion of embryonic development that are mosquito selective and represent potential targets for vector control. We performed bioinformatic analyses to identify putative protein-coding sequences that are specific to mosquito genomes. Systematic RNA interference (RNAi) screening of 40 mosquito- specific genes was performed by injecting double-stranded RNA (dsRNA) into female Aedes aegypti mosquitoes. This experimental approach led to the identification of eggshell organizing factor 1 (EOF1, AAEL012336), which plays an essential role in the formation and melanization of the eggshell. Eggs deposited by EOF1-deficient mosquitoes have nonmelanized fragile eggshells, and all embryos are nonviable. Scanning electron microscopy (SEM) analysis identified that exochorionic eggshell structures are strongly affected in EOF1-deficient mosquitoes. EOF1 is a potential novel target, to our knowledge, for exploring the identification and development of mosquito-selective and biosafe small-molecule inhibitors.