Parasitic fungi can take over a brain for their own benefit. It’s getting worse.

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

Around sunset, there is a sudden burst of movement when 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 lifts 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 muscaewhich translates to “destroyer of insects.” It is an obligate pathogen – completely dependent on its host – that 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.

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 analyze 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 as they get close, they start to smell some less volatile compounds from the carcasses – and that triggers sexual behavior.”

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 muscae that also attracts predators,” says Jensen, who has written an overview of it fungi that are pathogenic to insects in the Annual review of entomology. “It’s probably super nutritious!”

Fruit flies go on the victim list

Most research on zombie flies has focused on house flies, but Harvard molecular biologist and zombiologist Carolyn Elya turned her research to fruit flies after accidentally discovering some zombified specimens in her backyard while she was a PhD student at UC 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 melanogastera 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 Drosophila genetic 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 started to behave as if they were zombified.

Elya also discovered that the fly’s circadian neurons – the ones 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.

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. muscae genome. By focusing on the species that infects fruit flies, the scientists reported that they had found genes similar to the so-called white collar 1with instructions for making a blue light sensor in a mold called Neurospora crassa. In N. crassa, white collar 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 fully utilize the fly’s tissues and nutrients. These include specialized genes that encode trehalase enzymes, which digest trehalose, the primary sugar in hemolymph; proteins such as chitinases that break down chitin in the fly’s exoskeleton; and 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, ” says Elya. “Being able to specifically target every last tissue in their host is important.”

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, De Fine Licht, and colleagues reported their analysis of the RNA in housefly heads at different times after one E. muscae infection. 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 the activity of a fungal gene that is similar to the so-called fungal gene e.g that 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 e.g 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 UC Berkeley that Elya co-authored think that E. muscae may not work alone. The fungus appears to be infected with a virus while at the same time parasitizing 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. Another hypothesis, however, 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.

The 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 want 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.”

This article originally appeared in Well-known magazinean independent journalistic initiative of Annual Reviews. Register for the newsletter.