How a zombie fungus hijacks its host

A parasitic fungus that infects fruit flies and turns them into “zombies” has been studied in the laboratory for the first time. The fungus, Entomophthora muscae, whose name is derived from the Greek for “insect destroyer,” hijacks the nervous system of an infected host to use it for its own ends.

Carolyn Elya and her colleagues at UC Berkeley discovered a strain of the fungus in wild Drosophila flies and studied its infection process in the lab, using a combination of histological, molecular and genome-sequencing techniques. They reported their findings in a preprint in bioRxiv.

Elya first found the infected Drosophila that began the study almost by accident. At the time, she was using a bait trap to catch wild Drosophila to study their microbial loads. She stopped actively checking her bait for a few days, and when she returned she saw dead flies in the trap. They had died with their wings “stuck up away from their body,” she said. “I got excited and tossed some into a tube and sprinted to lab to check them under a scope.” She saw evidence of fungal growth and sporulation on the dead flies, which meant they had been infected by E. muscae. “I was super excited and absolutely stunned,” she said.

Elya’s lab had been interested in studying E. muscae “off and on for the past few years,”  but had had difficulty getting a project started for various reasons. They had collected wild Drosophila that were infected with the fungus previously, but couldn’t get other flies infected in the lab. When Elya found the dead flies in her trap, she knew they could be the key to getting the study going.

When E. muscae spores infect a fly, its mycelium grows into the fly’s nervous system, where it seizes control of its behavior. It directs the fly to crawl to an elevated place, grip it tightly with its proboscis and raise its wings in a “death pose.” The raised wings ensure that when the fungal growths called conidiophores sprout, they’ll have plenty of room to shower the surrounding area with new spores, infecting more flies.

The researchers genotyped the spores from a dozen dead flies to make sure they had been killed by E. muscae. When they found that the zombie fungus was the killer, Elya and her colleagues established a culture of it from one of the wild flies. To infect healthy lab-reared Drosophila, they housed them overnight in confined spaces with the cadavers of flies killed by the fungus. They observed the infection process and the behavior of the doomed flies over several days. In an infected fly, the first sign that death is imminent is that it loses the ability to fly.

“It’s really unsettling to watch the flies die,” said Elya. “They shake and struggle and it’s pretty awful. Putting them headfirst in agar felt wrong, even though when we did this they were definitely dead. We normally spend so much time trying to keep flies alive and happy in lab – everything about this felt off.”

“I still feel bad for the flies, but working with them for the past two years has desensitized me. I can observe their end-of-life behaviors now without getting chills. On the other hand, I’ve always found the fungus beautiful. The spores look like dew drops on the dead flies.”

The researchers mapped the progression of the fungal infection by culling samples of flies every 24 hours after exposure and sectioning them to see where the fungus had traveled. They found that it infiltrated the flies’ nervous systems early on in the course of infection, entering the brain within 48 hours. From there, the fungus could directly access the host’s neurons and manipulate its behavior.

Dros
Histology of infected Drosophila over 48 hours. From Elya et al.

“I was really surprised that the fungus is in the nervous system so early on in infection,” said Elya. “In zombie ants this isn’t the case. We can’t say at this point if being in the brain is significant mechanistically, but it puts the fungus in the right place at the right time for messing with neurons and therefore changing behavior.”

By surveying the gene expression in E. muscae across their exposed samples, the researchers were able to determine that there were three groups of genes that were expressed at different phases of the infection. Some 312 E. muscae genes are not activated until after the host has been killed. The products of the gene transcripts are currently unknown. The hosts showed gene expression patterns that were related to immune responses early in the infection, and genes related to cell function later in the infection.

“Understanding how the fungus changes fly behavior, whether it’s by directly changing the activity of all neurons, a few neurons or by causing a cascade of non-neuronal changes in the host that ultimately lead to neuronal changes, will expand our understanding of ways to change behavior,” said Elya. “It’s hard to say exactly what the repercussions will be, given that we don’t know how this thing works, but getting a better understanding of how to alter a brain to change animal behavior will be helpful long term.

“The most exciting thing is having this fungus in a host where we already know so much about its biology and can make such precise manipulations to understand how the host is being controlled,” she said.

 

 

 

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s