Zombie Ants: Microbial Mind-control Deep Within the Rainforest
Mind control isn’t just something from the movies or the latest graphic novel. In fact, it is a real-life phenomenon that exists among many species that inhabit our earth. The zombie fungus, Ophicordyceps unilateralis, hides deep within tropical rainforests and parasitizes upon ants from the Camponotini tribe.
Infection by the zombie fungus forces the ants to sacrifice themselves for fungal growth. While uninfected ants follow a foraging trail, infected ants do not. A week after being infected, the ants leave their home to climb upwards until they reach a point where the temperature and humidity are optimal for fungal growth. There, infected ants bite down into the undersides of leaves, lock their mandibles into plant tissue as muscles atrophy, and die. This "death grip" occurs only around noon. Soon, the infected ants transform into alien-like structures, sprouting fungal fruiting bodies from their heads that soon rupture to release a shower of spores that rains down on the forest floor. There, the fungal spores wait for the next meandering ant to fall victim to infection and bring the fungal life cycle full circle.O. unilateralis’s victim of choice is the carpenter ant (Camponotus leonardi ), though it is able to parasitize closely related Camponotini species. As their name suggests, carpenter ants craft homes out of wood, chewed out by their mandibles. But when infected with the zombie fungus, their mandibles serve another purpose: the "death grip," a signature hallmark of the infection.
But what goes on behind the scenes during this fungal infiltration? How does the fungus control the ant’s behavior? A group of scientists led by David Hughes of Penn State sought to understand changes within the infected ants' heads that could possibly explain the bizarre behaviors. These researchers infected ants with O. unilateralis and collected ant and fungal samples from ant heads during the course of infection. By identifying and quantifying RNA transcripts from the samples in a process known as RNA-seq, the group was able to determine how gene expression changed as the infection progressed.
The researchers focused on changes in gene expression during and after the leaf-biting behavior. Each stage in the infection was accompanied by distinct waves of gene expression. Many genes were upregulated during leaf biting and then became downregulated after the ant died. They found that 80% of the genes upregulated during infection are unique to O. unilateralis. In other words, there is a whole cadre of genes absent from insect pathogens that don't manipulate their hosts behavior and thus are predicted to play important roles in O. unilateralis behavior control. After the ant’s death, a different set of genes became upregulated as the fungus grew and sporulated.
Also during infection, the increased secretion of acid sphingomyelinases breaks down sphingolipids. Sphingolipids are found particularly in the myelin sheath that surrounds nerve cells, meaning that O. unilateralis is literally breaking down the ant’s nervous system. Alterations in sphingolipid composition in neurons can result in an altered signaling among neuronal cells.During infection, upregulated enterotoxins may interfere with the ant’s sensory response via chemosignaling. Infected ants are unresponsive to external stimuli, such as those that keep them along foraging trails. Hughes’s lab found that ant genes encoding receptors and binding proteins involved in smell and taste were downregulated during infection.
Changes in ant dopamine pathways also result from infection by the fungus. Dopamine, known to mediate aggressive behaviors in ants characterized by open-mandible threats and biting behaviors, may also be linked to the leaf-biting behavior during manipulation by the fungus.
After the ant dies, the fungus has a different task at hand: growth. While the fungus was manipulating the ant’s behavior, fungal sugar metabolism genes were downregulated. But after the ant dies, expression of genes related to pathogenicity decreases, and sugar metabolism surges as the fungus starts to multiply and sporulate.
Much of the research described here provides examples of how changes in gene expression link to behaviors, and further studies are needed to demonstrate causation. We have much to tease out about how microbes exert "mind control." In the meantime, remember that while Halloween only happens once a year, spookiness in all corners of the microbial world occurs every day.