Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo-Dioulasso, Burkina Faso.
Department of Entomology, University of Maryland, College Park, Maryland, 20742, USA.
Sci Rep. 2017 Jun 13;7(1):3433. doi: 10.1038/s41598-017-03399-0.
The continued success of malaria control efforts requires the development, study and implementation of new technologies that circumvent insecticide resistance. We previously demonstrated that fungal pathogens can provide an effective delivery system for mosquitocidal or malariacidal biomolecules. Here we compared genes from arthropod predators encoding insect specific sodium, potassium and calcium channel blockers for their ability to improve the efficacy of Metarhizium against wild-caught, insecticide-resistant anophelines. Toxins expressed under control of a hemolymph-specific promoter increased fungal lethality to mosquitoes at spore dosages as low as one conidium per mosquito. One of the most potent, the EPA approved Hybrid (Ca/K channel blocker), was studied for pre-lethal effects. These included reduced blood feeding behavior, with almost 100% of insects infected with ~6 spores unable to transmit malaria within 5 days post-infection, surpassing the World Health Organization threshold for successful vector control agents. Furthermore, recombinant strains co-expressing Hybrid toxin and AaIT (Na channel blocker) produced synergistic effects, requiring 45% fewer spores to kill half of the mosquitoes in 5 days as single toxin strains. Our results identify a repertoire of toxins with different modes of action that improve the utility of entomopathogens as a technology that is compatible with existing insecticide-based control methods.
疟疾防控工作的持续成功需要开发、研究和实施新的技术，以规避杀虫剂抗性。我们之前已经证明，真菌病原体可以为杀蚊或杀疟生物分子提供有效的输送系统。在这里，我们比较了节肢动物捕食者的基因，这些基因编码昆虫特异性的钠、钾和钙通道阻断剂，以评估它们提高对野生捕获的、具有杀虫剂抗性的按蚊的杀真菌效果的能力。在血淋巴特异性启动子的控制下表达的毒素，在孢子剂量低至每只蚊子一个分生孢子时，就能提高真菌对蚊子的致死率。其中最有效的一种是 EPA 批准的 Hybrid（Ca/K 通道阻断剂），用于研究其在致死前的效果。这些效果包括降低吸血行为，几乎 100%感染约 6 个孢子的昆虫在感染后 5 天内无法传播疟疾，超过了世界卫生组织成功控制病媒的阈值。此外，共表达 Hybrid 毒素和 AaIT（Na 通道阻断剂）的重组菌株产生协同作用，与单毒素菌株相比，在 5 天内杀死一半蚊子所需的孢子减少了 45%。我们的研究结果确定了一组具有不同作用模式的毒素，提高了昆虫病原真菌作为一种与现有的基于杀虫剂的控制方法兼容的技术的实用性。
