Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in Anopheles stephensi mosquitoes.
Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in Anopheles stephensi mosquitoes.
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DOI：
10.1371/journal.ppat.1001003
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发表时间：
2010-07-15
期刊：
影响因子：
6.7
通讯作者：
Riehle MA
中科院分区：
文献类型：
--
作者：
Corby-Harris V;Drexler A;Watkins de Jong L;Antonova Y;Pakpour N;Ziegler R;Ramberg F;Lewis EE;Brown JM;Luckhart S;Riehle MA
疟疾（疟原虫属）每年导致近一百万人死亡，而且随着药物和杀虫剂耐药性降低当前控制策略的有效性，这一数字可能还会增加。最重要的人类疟原虫恶性疟原虫在蚊子体内经历了一个复杂的发育周期，大约需要两周时间，并从入侵蚊子中肠开始。在这里，我们证明蚊子中肠中 Akt 信号传导的增加会扰乱寄生虫的发育，同时减少蚊子感染人类的持续时间。具体来说，我们发现杂合史氏按蚊中肠中 Akt 信号传导的增加使受感染的蚊子数量减少了 60-99%。在那些被感染的蚊子中，我们观察到寄生虫数量减少了 75-99%。在 Akt 信号增强的纯合蚊子中，寄生虫感染被完全阻断。中肠特异性 Akt 信号传导的增加也导致蚊子的平均寿命缩短 18-20%。因此，Akt 信号的激活减少了受感染蚊子的数量、每只受感染蚊子的疟原虫数量以及蚊子感染的持续时间。为了发生疟疾传播，蚊子必须摄入并寄生寄生虫大约两周，而寄生虫则完成多个发育阶段。在发育完成并且疟疾寄生虫侵入蚊子唾液腺之前，不会发生向其他宿主的传播。寄生虫发育完成后，随后的每次叮咬都有可能传播。在这项研究中，我们证明，蚊子中胰岛素信号传导所必需的单一活化蛋白激酶的组织特异性过度表达可以显着减少寄生虫的发育。这种激酶（Akt）被描述为调节一系列生理过程的关键细胞信号传导节点。除了对寄生虫发育的影响之外，相对于对照组，Akt 信号传导的增加还缩短了蚊子的平均寿命，从而限制了寄生虫成功传播的机会之窗。因此，我们证明对一种关键信号蛋白的基因操作可以直接减少昆虫媒介中寄生虫的发育以及蚊子感染的持续时间。
Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60–99%. Of those mosquitoes that were infected, we observed a 75–99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18–20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity. For malaria transmission to occur, a mosquito must ingest and harbor the parasites for approximately two weeks while the parasites complete multiple developmental stages. Until development is complete and the malaria parasites invade the mosquito salivary glands, transmission to another host cannot occur. Upon completion of parasite development, transmission is possible with every subsequent bite. In this study we demonstrate that tissue-specific overexpression of a single activated protein kinase that is essential to insulin signaling in the mosquito can dramatically reduce parasite development. This kinase – Akt – has been described as a critical cell signaling node that regulates a range of physiological processes. In addition to the impact on parasite development, increased Akt signaling also reduced the average mosquito lifespan relative to controls, thereby limiting the window of opportunity for successful parasite transmission. Thus, we demonstrate that genetic manipulation of one key signaling protein directly reduces parasite development in the insect vector as well as the duration of mosquito infectivity.
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影响因子：
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