Chinese Academy of Sciences (CAS) Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.
CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100049 Beijing, China.
Proc Natl Acad Sci U S A. 2021 May 11;118(19). doi: 10.1073/pnas.2023802118.
Chemical insecticides remain the main strategy to combat mosquito-borne diseases, but the growing threat of insecticide resistance prompts the urgent need to develop alternative, ecofriendly, and sustainable vector control tools. Entomopathogenic fungi can overcome insecticide resistance and represent promising biocontrol tools for the control of mosquitoes. However, insects have evolved robust defense mechanisms against infection. Better understanding of mosquito defenses against fungal infection is critical for improvement of fungal efficacy. Here, we show that as the pathogenic fungus penetrates into the host hemocoel, mosquitoes increase expression of the let-7 and miR-100 microRNAs (miRNAs). Both miRNAs translocate into fungal hyphae to specifically silence the virulence-related genes and , encoding a Rab guanine nucleotide exchange factor and a Zn(II)Cys transcription factor, respectively. Inversely, expression of a let-7 sponge (anti-let-7) or a miR-100 sponge (anti-miR-100) in the fungus efficiently sequesters the corresponding translocated host miRNA. Notably, strains expressing anti-let-7 and anti-miR-100 are markedly more virulent to mosquitoes. Our findings reveal an insect defense strategy that employs miRNAs to induce cross-kingdom silencing of pathogen virulence-related genes, conferring resistance to infection.
化学杀虫剂仍然是防治蚊媒疾病的主要策略，但杀虫剂抗性的日益威胁促使人们迫切需要开发替代的、环保和可持续的病媒控制工具。昆虫病原真菌可以克服杀虫剂抗性，是控制蚊子的有前途的生物防治工具。然而，昆虫已经进化出了强大的防御机制来抵御感染。更好地了解蚊子对真菌感染的防御机制对于提高真菌的功效至关重要。在这里，我们表明，当致病性真菌穿透宿主血腔时，蚊子会增加 let-7 和 miR-100 微 RNA（miRNA）的表达。这两种 miRNA 都转移到真菌菌丝中，特异性沉默与毒力相关的基因 和 ，分别编码 Rab GTP 交换因子和 Zn(II)Cys 转录因子。相反，在真菌中表达 let-7 海绵（anti-let-7）或 miR-100 海绵（anti-miR-100）可以有效地将相应转移的宿主 miRNA 隔离。值得注意的是，表达 anti-let-7 和 anti-miR-100 的 菌株对蚊子的毒力明显增强。我们的研究结果揭示了一种昆虫防御策略，即利用 miRNA 诱导跨物种沉默病原体毒力相关基因，从而赋予对感染的抗性。
