This parasitic fungus turns flies into zombie insects

The white substance on this fly is called a fungus Entomophthora muscae.
Filippo Castellucci

A fly does its job, buzzing here, buzzing there, but then it starts to behave strangely. His movements become slow; his belly swells. Its body produces white fluff.

Around sunset, there is a sudden burst of movement as the fly climbs (or ‘tops’) an elevated location, such as the top of a small plant or a stick, and extends its mouthparts. It spits out a sticky ooze that adheres it tightly to its perch, after which it raises its wings and dies.

Below, other unsuspecting flies are hit by a shower of white spores that shoot from the dead fly’s corpse. And the cycle starts all over again.

The white stuff that engulfs these flies is called a fungus Entomophthora muscae—Entomophthora translates to “destroyer of insects.” It is an obligate pathogen, completely dependent on its host, which infects flies and turns them into ‘zombies’ who do his bidding.

Discovered more than 160 years agothe fungus’ actions are as baffling as they are macabre. Scientists have long wondered: how does the fungus manage to keep flies under control? brain? How does it ‘know’ to do it at a specific time of day? What genes in his genome help him become a master manipulator?

Today, a series of experiments are beginning to unravel the science behind this creepy mind control.

Fatal necrophilia

Henrik H. De Fine Licht, an evolutionary biologist at the University of Copenhagen, is one of the few people in the world working with “zombie” house flies. Musca domestica. Although he was initially attracted to the fungus E. muscae Because he wanted to study obligate pathogens, “I was of course also fascinated by the aspects of behavioral manipulation and how that works,” he says.

Those details are like fodder for a horror movie. After the fungus infects the fly, it does not go directly to the vital organs, but first begins to consume fats and other nutrients, gradually starving the fly but keeping it alive. Only when it has no more non-vital organs to chew does it begin to control the fly’s behavior and thus ensure its continuity: by forcing the fly to seek a certain height and get stuck there, it ensures a wide distribution of its spores.

Life cycle of the fungus Entomophthora muscae

Adapted from HH De Fine Licht et al. / Author 2023 (preprint) / Knowable Magazine

The Fine Licht was particularly intrigued by reports describing how the fungus emerged manipulates flies by making female fly carcasses attractive to healthy males. The males fly in and try to mate with the infected carcasses – and promptly become infected themselves. To investigate the nature of this fatal attraction, De Fine Licht and his team ground up infected and uninfected fly carcasses to extract and analyze chemicals, and studied the air around the carcasses. They reported in 2022 that the mold releases volatile chemicals which lure the males in.

However, it is not entirely clear whether the volatile substances attract male flies with the promise of sex or nutrition, says De Fine Licht. A working hypothesis is that perhaps they are simply attracted because they think it is food. “But when they get close, they start to smell the less volatile components of the carcasses – and that triggers sexual behavior,” he says.

Annette Jensen, an organismal biologist at the University of Copenhagen, also noticed something intriguing about the way other insects responded to the smell of dead flies. She and one of her students discovered that the earwig – an insect that feeds on other insects – is attracted to the spore-forming fly carcasses infected by E. muscae and prefers to feed on it over uninfected carcasses or carcasses infected with other types of fungi. The scientists came to their conclusions after conducting experiments in which earwigs were placed between two types of carcasses and allowed to select which one to move to.

‘Maybe there’s something about the volatiles Entomophthora muscaethat also attracts predators,” says Jensen, who co-wrote an overview of it fungi that are pathogenic to insects in the Annual review of entomology. “It’s probably super nutritious!”

E. muscae-infected female carcasses emit volatile chemicals that attract unsuspecting male flies. The males try to mate with the female corpses and become infected. In this image, two male flies were attracted to the scent.

Filippo Castellucci

Fruit flies are added to the victim list

Most research on zombie flies has focused on house flies, but molecular biologist and zombiologist Carolyn Elya of Harvard University focused her research on fruit flies after accidentally discovering some zombified specimens in her backyard while she was a PhD student at the University of California, Berkeley. She had put out rotten fruit as bait to catch wild fruit flies for experiments and was surprised to see some dead fruit flies with their wings up in that telltale position, with white, fluffy trails on their bellies. She quickly analyzed some DNA from the spores and confirmed her suspicion: these fruit flies were victims of E. muscae.

Elya began to infect Drosophila melanogaster a proven laboratory model that researchers around the world have been studying for more than a century. With this E. muscae-D. melanogaster systemshe would like to take advantage of the powerful Drosophilagenetic toolkit and study the fly brain to understand how the fungus carries out its manipulation.

In a 2023 report, Elya and her colleagues showed that the fungus could secrete something into the fly’s ‘blood’ – the hemolymph –that helps manipulate fly neurons. When she injected the hemolymph from infected flies into uninfected flies, they began to behave as if they were zombified.

Elya also discovered that the fly’s circadian neurons – the neurons that help it keep track of its daily rhythm – may be involved in its time-sensitive altitude-seeking behavior. Silencing specific sets of these neurons in the brain inhibited spike activity in the infected flies.

E. muscae- infected “zombie” Drosophila Fruit flies behave similarly to house flies. This photo shows them climbing to the top of a stick and clinging to it with their mouthparts. They also raise their wings before dying so that the spores are properly distributed.

Carolyn Elya

Elya also wants to understand this mind control from the perspective of the fungus – and to that end she, De Fine Licht and others recently the enormous order E. muscaegenome. By focusing on the species that infects fruit flies, the scientists reported that they had found genes similar to the gene called “white collar 1,” which contains instructions for making a blue light sensor in a mold called Neurospora crassa. In N. crassa clerk 1 plays a role in circadian rhythms – and so the scientists hypothesize that this gene may be involved in determining the precise timing of infected flies’ topping behavior around sunset, followed by their death.

The scientists also discovered many genes that could help the fungus make full use of the fly’s tissues and nutrients. These include specialized genes that encode trehalase enzymes, which digest trehalose, the primary sugar in hemolymph; for proteins such as chitinases that break down chitin in the fly’s exoskeleton; and for lipases, which break down fats.

“That makes sense, right? Because these fungi are highly specialized in the way they use their hosts – not by killing them first and eating them later, which is a strategy used by many generalist pathogens, but instead they grow inside the insects, Elya says. say. “Being able to specifically target every last tissue in their host is important.”

And the search for more clues continues, with researchers going beyond the static genome and studying the RNA copies of genes that are made when specific genes are active. In a research paper yet to be peer-reviewed, Sam Edwards, a postdoctoral researcher at Wageningen University in the Netherlands, says; The Fine Light; and colleagues reported their analysis of the RNA in housefly heads at different times after one E. muscaeinfection. By figuring out which fly and fungal genes were active in the fly’s head, they hoped to get a glimpse of how the fungus manipulates the fly’s behavior.

The team discovered activity of a fungal gene similar to the gene called ecdysteroid UDP-glucosyltransferase, or “egt,” which is present in certain zombifying viruses. These viruses, such as E. muscae , force their infected victims – in this case caterpillars – to move to high locationsand in a move more gruesome than their fungal counterparts, cause the caterpillars to melt and release the underlying virus particles. The egt gene plays a role in this virus-induced caterpillar behaviorso the researchers now want to know if the gene is there E. muscae is the key to inducing bud formation in infected flies.

In a further twist, both the preprint of De Fine Licht and a recent study from the University of California, Berkeley, which Elya co-wrote think that E. muscae may not work alone. The fungus appears to be infected with a virus while it parasitizes house flies and fruit flies. However, whether this virus helps the fungus control the fly remains to be seen.

Elya, De Fine Licht and others all still want to know how the fungus starts to manipulate. One hypothesis is that E. muscae directly releases a chemical that activates the neurons involved in the fly’s apex behavior. But another hypothesis is that the all-consuming presence of the fungus, and the resulting physiological changes in the fly, trigger the fly’s own neurons to release chemicals to initiate the process.

De Fine Licht would like to see the zombie fly fungus system taught in schools to attract younger science enthusiasts. He and Edwards recently published instructions on how to observe the zombifying fungus in the laboratory. “It could encourage high school teachers and others to try this out, if they wanted to,” says De Fine Licht.

Part of this involves collecting fly carcasses from the field and isolating the fungus from them.

“Or you can try to infect some healthy flies in the laboratory by placing them together with the carcass,” says De Fine Licht. “That might be the best part, right? I try to observe zombie behavior in a small box.”

Well-known magazineis an independent journalistic initiative of Annual Reviews.

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Filed Under: Brain, Environment, Fungus, Insects, Nature,