In a typical home, a fly’s erratic buzz can often be a minor annoyance. But behind closed doors, a far more sinister fate may be unfolding for these common insects. An international team of scientists, led by researchers from the University of Copenhagen, has unveiled new insights into a fungus that transforms 60-80% of flies into what can only be described as zombies.

A Fungus with a Sinister Strategy

Entomophthora muscae, a fungus that has intrigued scientists for decades, has a unique modus operandi. It infects flies, eats them from the inside out, and manipulates their behavior in ways that serve its own lifecycle. The fungus forces the fly to ascend to a high point, cling to a surface, and then die. From this elevated perch, the fungus releases spores that can infect other flies, continuing the cycle.

Henrik De Fine Licht, a researcher at the University of Copenhagen, has been studying this fungus for years. Recently, he and his colleagues achieved a major breakthrough by mapping the fungus’s genome, which is about 25 times larger than that of most fungi. This genetic map offers a detailed look at the biological arsenal the fungus uses to hijack its hosts.

“The genome is a catalog of all the genes found in the fungus,” says De Fine Licht. “Such a catalogue can better equip us to look at which genes are active in a fly’s brain at the point when the fungus transforms it into this zombie-like state. And in this way, we hope to understand how it can do such a wild thing”

The Mechanics of Mind Control

The fungus’s life cycle is as gruesome as it is fascinating. Once a fly is infected, the fungus slowly consumes it from within, leaving the insect alive until almost all of its nutrients are drained. Then, it seizes control of the fly’s brain, compelling it to climb upwards. At this point, nearly the entire fly is replaced by fungal mass. The fly becomes little more than a vessel, its natural behaviors replaced by the fungus’s commands.

After the fly dies, the fungus begins ejecting spores from the corpse, all while releasing a chemical lure that attracts healthy flies. But the bizarre spectacle doesn’t end there. These flies, attracted by sex pheromones, attempt to mate with the infected dead, allowing the fungus to infect a new host.

Previously, a 2022 study led by De Fine Licht found that 73% of the male flies mated with female fly carcasses that had died from the fungal infection 25-30 hours earlier, whereas only 15% of the males mated with females that had been dead for only 3-8 hours. It’s a grotesque yet highly effective strategy for spreading the infection.

Carolyn Elya, a biologist from Harvard University and co-author of the study, points out that the fungus operates with a remarkable sense of timing. “The behavioral manipulation always begins at dusk,” Elya notes. “This is likely because the humidity is higher at night, which helps preserve the spores.”

This precision suggests a complex interaction with the environment, hinting at light-sensitive proteins within the fungus that may be detecting time cues. Lo and behold, the newly sequenced genome reveals these proteins, providing new avenues for understanding how the fungus’s behavior-timing mechanism works.

The mapped genome also revealed genes that code for enzymes that break down the hard chitin shells of insects.

“This reflects that the fungus has a unique evolutionary adaptation to grow and live in insects. While unsurprising, it has now been verified for the first time,” says Elya.

Implications Beyond the Fly Kingdom

While the study of a fly-killing fungus might seem like a niche endeavor, the implications could be far-reaching. The researchers believe that understanding how Entomophthora muscae controls fly behavior might provide insights into broader questions of neurology and psychotropic drug development.

“Understanding how the human brain works in relation to behaviour is often a challenge because it is difficult to measure precisely. But here, we have a system with a very defined behavior that we know is controlled by a fungus in the brain of an insect. If we understand how the fungus operates, we can begin to map the entire sequence from genes and molecules to behavior,” says De Fine Licht, who added:

“And then, one may be inspired by the chemical substances and certain mechanisms that the fungus deploys to manipulate the fly’s behaviour when, for example, designing new drugs for mental illnesses in humans.”

The potential applications don’t stop at medicine. The fungus’s specificity could make it a valuable tool for biological pest control. Current pesticides often harm a broad range of insects, including beneficial species like bees. A fungus-based insecticide, however, could offer a more targeted approach, reducing collateral damage to non-pest insects.

“So, if further research leads to the development of an insecticide based on this fungus, which has the great advantage of only attacking one species of fly, it would be very, very attractive,” concludes Henrik de Fine Licht.

The research is still in its early stages, but the genetic map provides a solid foundation for further exploration. As scientists delve deeper into the genes of Entomophthora muscae, they hope to unlock even more secrets of this mind-controlling organism.

For now, it’s a waiting game. But with each discovery, we move closer to harnessing — or at least understanding — the powerful and eerie tactics of nature’s own puppet master.

The findings appeared in the journal eLife.