Insects export microRNAs to fungal pathogen to silence virulence genes and confer antifungal defense

The growing threat of mosquito insecticide resistance prompts the urgent need to develop alternative eco-friendly vector control tools. Entomopathogenic fungi can overcome insecticide resistance and show promise for mosquito control. Improvement of fungal efficacy requires better understanding of mosquito-fungus interactions. Here, we show that host insects increase the expression of let-7 and miR-100 after B. bassiana infection, and export both miRNAs into fungal cells to specifically silence virulence genes sec2p encoding a Rab guanine nucleotide exchange factor and C6TF encoding a Zn(II)2Cys6 transcription factor, respectively. Importantly, B. bassiana strain expressing both anti-let-7 and anti-miR-100 is markedly more virulent to mosquitoes. Together, our findings reveal a novel insect defense strategy of delivering miRNAs into fungal pathogens to induce cross-kingdom silencing of virulence-related genes and confer resistance to fungal infection.