Entomophthora muscae: destroyer of flies

I study a entomopathogenic zoopagomycete fungus called Entomophthora muscae that infects fruit flies, then, right before killing them, manipulates their behavior to help spread to a new host. This fungus was first described in the scientific literature 1855 by Ferdinand Cohn, though it was known well before his publication. E. muscae is in fact just one of several entomophthoralean fungi that make their living infecting, behaviorally-hijacking and killing insect hosts. Though E. muscae’s MO is eerily similar to that of Ophiocordyceps spp., who are responsible for the infamous “zombie ant”, this fungus is about as distantly related as you and I are from our fruit fly friends.

Zombies are real

Figure 1. An E. muscae-killed fruit fly, aka a zombie fly.

E. muscae begins its journey when an infectious spore, also called a conidium, lands on the cuticle of a fly host. The spore then employs specialized enzymes to burrow through the cuticle to reach the hemolymph-filled open circulatory system of the insect. Now inside, the fungus helps itself to the fly’s reserve nutrient stores called the fat body (a tissue that functions similarly to vertebrate liver). The fungus continues this way, leaving the fly’s organs (nervous system, muscles, gut and gonads) intact as it exhausts these nutrient stores. During this time, the fly continues to behave essentially normally, eating, mating and living its best fly life.

Once the fat body is gone, the fungus initiates its escape plan: it lifts the organ embargo and dines on the gut and gonads (note: the fly is still very much alive at this point!) then somehow elicits a series of very specific behaviors in its fly host. Importantly, this series of events is always timed to coincide with sunset.

First, the fly climbs to an elevated location (a phenomenon known as “summit disease”).

Next, the fly extends its proboscis to make contact with whatever surface it’s standing upon. Fungal growths emanating from the proboscis serve to glue the proboscis down, keeping the fly stuck in place.

Finally, the wings of the fly lift up and away from its back, conveniently clearing a path for the fungus to make its dramatic exit.

While the fly has been positioning itself on the fungus’ behalf, the fungus has been preparing for departure, growing structures called conidiophores that, once the host is dead, will pierce through the cuticle, grow out of the fly, then form and launch an infectious spore.

Once mature, this spore is fired as if from a squirt gun into the environment.

Aside from their initial launch, the spores are not motile: they rely on wind to carry them to a suitable host. By having positioned the dying fly up high, the fungus can ride the breeze to cover the largest possible area, and thus reach the most possible hosts in the vicinity.

If the spore fails to land on a target, it can give it another go by forming a secondary conidium (similar to a primary conidium, but smaller) and launching again into the wild.

Usually, the fungus stops there, but sometimes can go on to form tertiary and even higher-order spores in its attempt to reach a new host.

My research interests

Generally, I’m fascinated by anything related to behavior-manipulating parasites, like Entomophthora muscae and its behavior-manipulating fungal cousins. The most burning question I want to answer is: how do these parasites control host behavior? As a postdoctoral researcher, I’m working to understand the neurobiological basis of behavior manipulation in zombie flies. In particular, I’m interested in understanding what fly neural circuits the fungus hijacks to make sick flies summit prior to death and what chemicals the fungus employs to achieve this hijacking. Unlike proboscis extension or wing raising, summiting behavior cannot be simply explained by mechanics alone – the complexity of summiting (figuring out which way is up and coordinating how to get oneself there) belies its neuronal basis. Using a combination of fly genetics, automated high-throughput behavior and -omics approaches, I’ve established a neuro-mechanistic framework explaining how summiting comes to pass. Many questions still remain, both with respect to summiting and to the causal basis of other E. muscae-induced behaviors. I hope by understanding mechanisms of behavior manipulation within the experimentally-tractable zombie fly system, we can gain general insights into the strategies by which parasites hijack host behavior, and more broadly, principles underlying the generation of animal behavior as well as host-parasite co-evolution.

Learn more

Elya C, Lavrentovich D, Lee E, Pasadyn C, Duval J, Basak M, Saykina V, de Bivort BL. 2023. Neural mechanisms of parasite-induced summiting behavior in “zombie” Drosophila. Elife 12:e85410. doi:10.7554/eLife.85410

De Fine Licht HH, Edwards S, Elya C. 2023. Evolutionary ecology of an obligate and behaviorally manipulating insect- pathogenic fungus, Entomophthora muscae. Authorea Preprints. doi:10.22541/au.167778641.14505987/v1

Elya C, De Fine Licht HH. The genus Entomophthora: bringing the insect destroyers into the twenty-first century. IMA Fungus. 2021;12: 1–31. doi:10.1186/s43008-021-00084-w

de Bekker C, Beckerson WC, Elya C. Mechanisms behind the Madness: How Do Zombie-Making Fungal Entomopathogens Affect Host Behavior To Increase Transmission? MBio. 2021;12: e01872–21. doi:10.1128/mBio.01872-21

Wang JB, Elya C, St. Leger RJ. Genetic variation for resistance to the specific fly pathogen Entomophthora muscae. Sci Rep. 2020;10: 1–6. doi:10.1038/s41598-020-71262-w

Elya C, Lok TC, Spencer QE, McCausland H, Martinez CC, Eisen M. Robust manipulation of the behavior of Drosophila melanogaster by a fungal pathogen in the laboratory. Elife. 2018;7. doi:10.7554/eLife.34414

Coyle MC, Elya C, Bronski MJ, Eisen MB. Entomophthovirus: An insect-derived iflavirus that infects a behavior manipulating fungal pathogen of dipterans. bioRxiv. 2018. p. 371526. doi:10.1101/371526