Mechanisms behind the Madness: How Do Zombie-Making Fungal Entomopathogens Affect Host Behavior To Increase...

Transmission is a crucial step in all pathogen life cycles. As such, certain species have evolved complex traits that increase their chances to find and invade new hosts. Fungal species that hijack insect behaviors are evident examples. Many of these "zombie-making" entomopathogens cause their hosts to exhibit heightened activity, seek out elevated positions, and display body postures that promote spore dispersal, all with specific circadian timing. Answering how fungal entomopathogens manipulate their hosts will increase our understanding of molecular aspects underlying fungus-insect interactions, pathogen-host coevolution, and the regulation of animal behavior. It may also lead to the discovery of novel bioactive compounds, given that the fungi involved have traditionally been understudied. This minireview summarizes and discusses recent work on zombie-making fungi of the orders Hypocreales and Entomophthorales that has resulted in hypotheses regarding the mechanisms that drive fungal manipulation of insect behavior. We discuss mechanical processes, host chemical signaling pathways, and fungal secreted effectors proposed to be involved in establishing pathogen-adaptive behaviors. Additionally, we touch on effectors' possible modes of action and how the convergent evolution of host manipulation could have given rise to the many parallels in observed behaviors across fungus-insect systems and beyond. However, the hypothesized mechanisms of behavior manipulation have yet to be proven. We, therefore, also suggest avenues of research that would move the field toward a more quantitative future.