Tryptamine accumulation caused by deletion of MrMao-1 in Metarhizium genome significantly enhances insecticidal virulence

Abstract

Metarhizium is a group of insect-pathogenic fungi that can produce insecticidal metabolites, such as destruxins. Interestingly, the acridid-specific fungus Metarhizium acridum (MAC) can kill locusts faster than the generalist fungus Metarhizium robertsii (MAA) even without destruxin. However, the underlying mechanisms of different pathogenesis between host-generalist and host-specialist fungi remain unknown. This study compared transcriptomes and metabolite profiles to analyze the difference in responsiveness of locusts to MAA and MAC infections. Results confirmed that the detoxification and tryptamine catabolic pathways were significantly enriched in locusts after MAC infection compared with MAA infection and that high levels of tryptamine could kill locusts. Furthermore, tryptamine was found to be capable of activating the aryl hydrocarbon receptor of locusts (LmAhR) to produce damaging effects by inducing reactive oxygen species production and immune suppression. Therefore, reducing LmAhR expression by RNAi or inhibitor (SR1) attenuates the lethal effects of tryptamine on locusts. In addition, MAA, not MAC, possessed the monoamine oxidase (Mao) genes in tryptamine catabolism. Hence, deleting MrMao-1 could increase the virulence of generalist MAA on locusts and other insects. Therefore, our study provides a rather feasible way to design novel mycoinsecticides by deleting a gene instead of introducing any exogenous gene or domain. Mycoinsecticides are widely used in place of chemical pesticides to protect crops from pest damage. Metarhizium spp. fungi specifically live inside the body cavity of insects and can produce insecticidal metabolites, such as beauvericin, destruxins, and taxol. The variable virulence between host-generalist fungus Metarhizium robertsii (MAA) and host-specialist fungus Metarhizium acridum (MAC) to locusts was studied. We found that MAC is more virulent than MAA on locusts, and MAC-infected locusts display higher amounts of tryptamine than do MAA-infected locusts. Furthermore, MAC cannot produce destruxins, but can produce abundant tryptamine to kill locusts when accumulated owing to the absence of a gene for tryptamine catabolism in the MAC genome. Tryptamine activates the aryl hydrocarbon receptor of locusts (LmAhR) that produces damaging effects by regulating reactive oxygen species production and suppressing the immune system of locusts. Therefore, the deletion of MrMao-1 in the generalist fungus MAA significantly improves the virulence of the fungus to locusts and other insect species. The resulting new insights into the core metabolism of high virulence of host-specialist fungus can provide an improved basis for designing mycoinsecticide strains.