Department of Chemistry and Biochemistry, The University of Arizona, Tucson, Arizona, United States of America.
Department of Chemistry, San José State University, San José, California, United States of America.
PLoS Biol. 2019 Jan 8;17(1):e3000068. doi: 10.1371/journal.pbio.3000068. eCollection 2019 Jan.
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.
蚊媒疾病每年在全球导致数百万人死亡。控制蚊子种群的一种方法是破坏分子过程或拮抗新的代谢靶标，这些靶标对于产生有活力的卵是必需的。为此，我们专注于鉴定完成胚胎发育所需的蛋白质，这些蛋白质对蚊子具有选择性，是潜在的蚊虫控制靶点。我们进行了生物信息学分析，以鉴定特定于蚊子基因组的假定蛋白编码序列。通过向雌性埃及伊蚊注射双链 RNA (dsRNA)，对 40 个蚊子特异性基因进行了系统的 RNA 干扰 (RNAi) 筛选。这种实验方法鉴定了卵壳组织因子 1 (EOF1，AAEL012336)，它在卵壳的形成和黑化中起重要作用。缺乏 EOF1 的蚊子产下的卵没有黑化的脆弱卵壳，所有的胚胎都没有活力。扫描电子显微镜 (SEM) 分析表明，EOF1 缺陷蚊子的外卵壳结构受到严重影响。EOF1 是一个潜在的新靶点，据我们所知，可用于探索鉴定和开发蚊子选择性和生物安全的小分子抑制剂。
