Disrupting Mosquito Reproduction and Parasite Development for Malaria Control.
Disrupting Mosquito Reproduction and Parasite Development for Malaria Control.
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DOI：
10.1371/journal.ppat.1006060
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发表时间：
2016-12
期刊：
影响因子：
6.7
通讯作者：
Catteruccia F
中科院分区：
文献类型：
--
作者：
Childs LM;Cai FY;Kakani EG;Mitchell SN;Paton D;Gabrieli P;Buckee CO;Catteruccia F
用杀虫剂处理过的蚊帐和室内残留喷雾剂控制蚊子数量仍然是减少和消除疟疾方案的基石。然而，鉴于蚊子对杀虫剂的普遍抗药性，迫切需要减少蚊子媒介传播的替代战略，包括确定通过不同于速效杀虫剂的机制影响媒介能力的安全化合物。在这里，我们表明，针对类固醇激素信号传导的化合物破坏了多种生物过程，这些生物过程是蚊子传播疟疾能力的关键。当类固醇激素20-羟基蜕皮激素（20 E）的激动剂应用于冈比亚按蚊雌性时，冈比亚按蚊是撒哈拉以南非洲的主要疟疾蚊子媒介，它大大缩短了寿命，阻止了受精和产卵，并显著阻止了恶性疟原虫的发育，这三个组成部分对疟疾传播至关重要。模拟这些影响对按蚊种群动态和疟原虫传播的影响预测，使用20 E激动剂破坏类固醇激素信号传导将影响疟疾传播到与杀虫剂类似的程度。因此，操纵20 E途径提供了一种强有力的新方法来解决蚊子媒介传播疟疾的问题，特别是在受杀虫剂耐药性传播影响的地区。控制蚊虫是唯一能够将疟疾传播从非常高的水平降低到接近零的干预措施。然而，目前的蚊子控制方法受到传播疟疾的疟原虫的按蚊种群中杀虫剂抗性迅速蔓延的严重威胁。在这里，我们表明，当雌按蚊类固醇激素信号被中断时，其生命周期的各个方面都被打乱了--雌蚊产卵和产卵较少，交配不成功，死亡更快。此外，他们感染疟疾寄生虫的可能性也会降低。当我们模拟类固醇激素激动剂对疟疾传播的影响时，我们预测这些化合物将提供一种重要的抗疟疾新工具，特别是在广泛的杀虫剂耐药性地区。
The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E) is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance. Mosquito control is the only intervention that can reduce malaria transmission from very high levels to close to zero. However, current mosquito control methods are severely threatened by the rapid spread of insecticide resistance in anopheline mosquito populations that transmit the malaria-causing Plasmodium parasites. Here we show that when steroid hormone signaling is interrupted in female Anopheles mosquitoes, various aspects of their lifecycle are disrupted—females produce and lay fewer eggs, do not mate successfully and die more rapidly. Furthermore, they become less likely to be infected by malaria parasites. When we model the impact of steroid hormone agonists on malaria transmission, we predict that these compounds would provide an important new tool against malaria, particularly in regions of widespread insecticide resistance.
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影响因子：
3.3
作者：
Fillinger, U;Sonye, G;Becker, N
通讯作者：
Becker, N
影响因子：
3.9
作者：
Galikova, Martina;Klepsatel, Peter;Flatt, Thomas
通讯作者：
Flatt, Thomas
影响因子：
3
作者：
Depinay, JMO;Mbogo, CM;McKenzie, FE
通讯作者：
McKenzie, FE
DOI：
10.4269/ajtmh.2003.68.366
发表时间：
2003-03-01
影响因子：
3.3
作者：
Collins, WE;Jeffery, GM
通讯作者：
Jeffery, GM
影响因子：
3
作者：
Charlwood, JD;Pinto, J;Sousa, CA;Ferreira, C;Petrarca, V;Rosario, VD
通讯作者：
Rosario, VD