In 1855, scientists discovered a fungus that turns flies into zombie hosts. More than 160 years later, its spores still show how a parasite can control behavior in flies

A fly suddenly begins acting strangely. It becomes sluggish, its abdomen swells and white fuzz starts covering its body. Then, around sunset, it climbs to a high point, attaches itself to the surface and dies with its wings raised. What happens next is even more disturbing. Spores burst from the dead fly and spread to other flies below, beginning another cycle of infection, as per a report by Knowable Magazine.

The culprit is Entomophthora muscae, a parasitic fungus whose name translates to “destroyer of insects.” More than 160 years after its discovery, scientists are still trying to understand how this fungus takes control of its hosts and turns ordinary flies into what researchers describe as “zombies.”

How does the fungus control flies?

Entomophthora muscae does not simply kill a fly and consume its body. It depends entirely on its host and initially feeds on fats and other nutrients while keeping the insect alive.

As the infection progresses, the fungus eventually begins influencing the fly's behavior. The infected insect is driven to climb to an elevated location, where it attaches itself and dies. The position gives the fungus an effective way to release its spores over other flies.

Henrik H. De Fine Licht, an evolutionary biologist at the University of Copenhagen, has spent years studying these infected houseflies. He was initially interested in obligate pathogens, but the fungus's ability to manipulate behavior quickly became another major attraction.

“I was, of course, also fascinated by the behavioral manipulation aspects and how that works,” he says.

The fungus has another disturbing trick. Infected female fly carcasses can become attractive to healthy males. The males approach the dead females and attempt to mate with them, exposing themselves to infection.

De Fine Licht and his colleagues investigated this behavior by analyzing chemicals from infected and uninfected fly carcasses and examining the air surrounding them. Their 2022 research found that the fungus releases volatile chemicals that attract male flies.

It remains unclear whether the males initially approach because they mistake the carcass for food or because they are attracted sexually. De Fine Licht suggested that less-volatile chemicals encountered at close range may trigger the mating response.

Why are other insects attracted?

The strange chemical signals surrounding infected flies may not affect only potential mates.

Annette Jensen, an organismal biologist at the University of Copenhagen, and one of her students found that earwigs were attracted to fly carcasses infected with E. muscae. The earwigs also preferred these infected flies over uninfected carcasses or carcasses infected by other fungi.

The researchers reached that conclusion through experiments in which earwigs were given a choice between different types of fly carcasses.

“There might be something with the volatiles from Entomophthora muscae  that also attracts predators,” says Jensen, who co-wrote an overview of fungi that are pathogenic to insects in the Annual Review of Entomology. “It’s probably super nutritious!”

The discovery adds another layer to the fungus's unusual relationship with its host and the insects surrounding it.

Can the fungus turn fruit flies into zombies?

Most research on zombie flies initially focused on houseflies, but Harvard University molecular biologist Carolyn Elya became interested in fruit flies after finding infected flies in her backyard while she was a PhD student at the University of California, Berkeley.

She had been using rotten fruit to attract wild fruit flies when she noticed dead flies displaying the characteristic position, with their wings raised and white spores covering their abdomens.

DNA sequencing of the spores confirmed that the flies had been infected with E. muscae.

Elya then developed a system using Drosophila melanogaster, the well-established laboratory fruit fly. Because scientists have extensively studied the genetics of this species, the system provides researchers with a way to examine the fly brain and investigate how the fungus changes behavior.

In a 2023 report, Elya and her colleagues found evidence that something in the hemolymph, or “blood,” of infected flies could influence neurons. When hemolymph from infected flies was injected into healthy flies, the healthy insects began behaving as though they had been infected.

Elya also found that specific circadian neurons may play a role in the fungus's carefully timed behavior. Silencing certain groups of these neurons prevented infected flies from carrying out their characteristic summiting behavior.

Why does the timing matter?

One of the biggest mysteries surrounding E. muscae is how it appears to control the timing of the fly's final climb.

The infected insects often summit around sunset. Researchers studying the fungus's large genome have found genes similar to white-collar 1, a gene involved in producing a blue-light sensor in the mold Neurospora crassa.

Because white-collar 1 is involved in circadian rhythms in that mold, researchers hypothesize that a similar gene in E. muscae could help explain why infected flies climb at such a precise time of day.

The genome also contains genes that appear suited to extracting nutrients from the fly. These include genes for trehalase enzymes, which digest trehalose in hemolymph, along with chitinases that break down chitin and lipases that break down fats.

“That makes sense, right? Because these fungi are very specialized in the way that they utilize their hosts—not by killing them first and then eating them later, which is a strategy that’s used by a lot of generalist pathogens—but instead they grow inside of the insects,” Elya says. “Being able to specifically target every last tissue in their host is important.”

What are scientists still trying to discover?

Researchers are now moving beyond simply studying the fungus's genome. They are examining RNA copies of genes to determine which genes become active during different stages of infection.

A research paper that had not yet been peer-reviewed, involving Sam Edwards of Wageningen University, De Fine Licht and colleagues, examined RNA in housefly heads at different points following infection. The researchers were looking for patterns in both fly and fungal gene activity that could reveal how the fungus alters behavior.

The team identified activity in a fungal gene resembling ecdysteroid UDP-glucosyltransferase, or egt, which is also found in certain viruses known for manipulating infected caterpillars into climbing to high locations.

Researchers now want to determine whether the E. muscae version of the gene has a similar role in making infected flies summit.

There is another mystery. Research by De Fine Licht and a recent University of California, Berkeley, study co-authored by Elya indicate that E. muscae itself may be infected by a virus. Whether that virus helps the fungus control flies remains unknown.

Scientists are also considering two possibilities for how the manipulation begins. The fungus might release a chemical that directly activates neurons controlling summiting. Alternatively, the fungus's growth and the physiological changes it causes could trigger the fly's own neurons to start the process.

For De Fine Licht, the bizarre fungus could even become a useful way to introduce students to biology. He and Edwards have published instructions for observing the zombifying fungus in laboratory settings.

The research may be unsettling, but the tiny infected flies are giving scientists an unusual window into one of nature's strangest examples of behavioral control.

FAQs

What fungus turns flies into zombies?
Entomophthora muscae.

Why do infected flies climb?
To spread the fungus's spores.