The fungus that makes ‘zombie ants’ could use biological clocks to control their minds

Posted on May 24, 2017   by Anand Jagatia

The world of parasites can sometimes be extremely gruesome. Take, for example, the charming female jewel wasp, which uses a cockroach as a living incubator for its larvae. The wasp stings the roach in the brain, and leads the much bigger host by its antennae into a burrow before laying an egg inside its abdomen. The cockroach, being completely under the jewel wasp’s spell, doesn’t protest. Once the egg hatches, the larva consumes the cockroach from the inside out. Lovely.

Or how about the delightful horsehair worm? The larvae of this species get eaten by small insects like mosquitoes, which are themselves gobbled up by bigger bugs like crickets. Once inside its host, the larva matures into a beautiful butterfly foot-long worm. It then hijacks the cricket’s behaviour, causing it to jump straight into the nearest water source and drown itself. The worm emerges underwater in a writhing mass from the cricket’s abdomen, before mating and starting the cycle anew. (You can watch this happen in the video below – but be warned, this is something you cannot unsee.)

This kind of mind bending isn’t limited to animals. Toxoplasma gondii is a protist that famously makes rats attracted to cat urine (bad news for the rodent, good news for the parasite). But probably one of the most bizarre examples are fungi of the species complex Ophiocordyceps unilateralis, which infect and produce so-called ‘zombie ants’.

Ophiocordyceps spores infect carpenter ants while they are out at night searching for food. The fungus grows inside the ant and eventually causes it to leave the nest, seek out a piece of vegetation and climb it (all while convulsing horribly, of course). Once it’s ascended to a particular height, the ant clamps down with its powerful jaws and remains there until it dies, whereupon the fungus consumes it and uses the energy to produce a fruiting body. This structure bursts forth from the ant’s head like something out of a Ridley Scott film, and will rain down spores onto more unsuspecting ants below.

So what’s going on here? How does the fungus manage to pull off this amazing/terrifying piece of brainwashing? Charissa de Bekker is an Assistant Professor from the University of Central Florida who works on Ophiocordyceps, and gave a talk on her research at our Annual Conference last month.

“There are many different fungal species, and as far as we know each ant species gets infected by its own fungus,” says Charissa. “It’s very specific. There has been a long co-evolution between the parasite and the host, an arms race where the host is trying to get rid of the parasite, and the parasite is trying to overcome the immune system and strategies of the host.”

This battle has been going on for millions of years, and seems like the fungus has come out on top. It has developed the ability to subtly and precisely manipulate the ant’s behaviour, albeit in an extremely macabre way. For example, different ant species will be forced to seek out different plants and will latch onto specific parts, like a leaf or a twig. It’s only after this point that the fungus will enact its grizzly execution.

“When the fungus is inside the ant, it’s normally in a yeast-like state, living as single cells. But as soon as the ant dies, the fungus starts to produce hyphae, which form a big branching network of cells,” explains Charissa. “And if we look at the genes at this point, comparing when biting has taken place to when the ant has died, we see that the fungus quickly changes which ones it’s using.”

Using this approach, Charissa’s group is trying to figure out the molecular basis of this mind control. By infecting ants in the lab, following their behavior and looking at the genes expressed at different time points, it’s possible to piece together what’s happening inside both organisms.

“The way we do this is collect the heads of the ants, mash them up, get the RNA out and sequence it,” she says. “Then we map that back to the ant and the fungus.”

The lab has found that, after infection, the fungus starts to secrete a number of compounds into the ant, including enzymes that are known to enhance locomotive activity, and alkaloids that may be activating or deactivating receptors in the brain. As you might expect, after the ant has died, the fungus moves from creating compounds that manipulate behaviour to enzymes that can digest the victim’s innards.

Charissa’s latest work is also looking at the role that internal biological clocks, known as circadian rhythms, play in the fungus–ant interactions, as lots of aspects of the system seem to be tied to a certain time of day. For example, the Hughes Lab at Penn State, where Charissa did her postdoc, found that ants tend to bite down on the vegetation at solar noon, and that death follows swiftly a couple of hours later. The fungus only releases spores at a specific time of night when the ants are out foraging – and foraging behaviour is itself controlled by the insect’s circadian rhythms.

“So there’s all these different elements that made me think that a biological clock could be very important for this interaction,” says Charissa. “The fungus might be breaking into the behavioural output of the biological clock of the host, and maybe hijacking and taking advantage of it.”

The team has also learnt that the fungus has its own molecular clock, and contains versions of proteins known to be used for cycling in other fungal species. This may be important for orchestrating changes in the host.

“We’re definitely at the beginning of the exciting stuff,” says Charissa. “Most of the parasites we know about that change behaviour aren’t model organisms, so they haven’t been studied for as long as fruit flies or E. coli. But with sequencing technology, we have doors open, and we can actually start to look into what might be going on. It’s a very exciting, novel field.”