"Ant killed by fungus" by Bernard DUPONT via Wikimedia Commons is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license https://creativecommons.org/licenses/by-sa/2.0/ "Ant killed by fungus" by Bernard DUPONT via Wikimedia Commons is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license https://creativecommons.org/licenses/by-sa/2.0/

Imagine your body being manipulated like a puppet while your conscious brain watches. For some species of ants, this seemingly sci-fi scenario is a frequent reality. A handful of fungi have the unique ability to hijack the nervous systems of an insect host, invading its tissue and directing its movement while slowly eating the organism from the inside.

Penn State researchers have recently discovered the haunting details behind this unique example of parasitism. Using the fungal species complex Ophiocordyceps unilateralis, researcher Maridel Fredericksen and her colleagues have shown the extent to which microscopic fungal spores come to take over an ant’s body, gargantuan in comparison. When a spore of O. unilateris lands on a species of carpenter ant (Camponotus castaneus), it penetrates the insect’s exoskeleton and enters the circulatory system as a free-floating cell. Within just 16-25 days the fungus has spread throughout the ant’s body. Aggregates of cells induce the ant to climb upwards towards the light and anchor its jaw into a leaf. After that point, the fungus kills its host and releases new spores to continue the cycle of infection. Questions remain, however, about the extent of the fungal invasion into the ant’s body.

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Using cutting-edge microscopy techniques, Fredericksen has illustrated in detail the growth of the fungus within the ant’s body. Cells of O. unilateralis begin growing into a complex, multicellular networks, collectively called a mycelium, that concentrates in the ant’s jaw and inside its legs. What is surprising is that the brain, although surrounded by an abundance of fungal cells, is preserved.

How then does the fungus “take over” the ant’s body? Does the fungus act like a puppet-master, moving the ant from the inside to its desired location? Fine-scale imaging shows filament-like fungal cells grow in-between degraded muscle fibers, and begin to cooperate by fusing with one another. This is a common phenomenon in the bizarre world of fungi: filament-like cells from a single individual, or even multiple ones, can merge to create a complex network of cells with sometimes hundreds of interconnections. In the case of O. unilateralis, this is likely a means of synchronizing its manipulation of the ant’s body –– an “ant zombie” of sorts.

Rather than directly moving the limbs of the ant, O. unilateralis secretes a cocktail of chemicals, referred to as secondary metabolites, designed to commandeer a host’s behavior. More creepily, the fungus detects brains versus muscle, as the chemical profile of the fungus differs depending on which ant tissue it is infecting. While it is still a mystery why the fungus avoids colonizing the brain, indirect evidence from differing metabolite profiles suggests that the fungus seizes control of the ant’s existing nervous system via chemical signals, essentially taking the insect hostage from the inside out.

Fascinatingly, the extreme life cycle of O. unilateralis is not entirely unique, and there are examples of distantly related parasites showing surprisingly analogous behaviors. These similarities are an extreme example of “convergent evolution,” a biological phenomenon most often exemplified by a comparison between the wings of birds and bats. After millions of years of evolution, the morphologies of bird and bat limbs closely resemble each other to achieve a common goal, flight, despite being from two distantly related phyla. Hundreds of examples of convergent evolution exist across the tree of life, but the parasites’ ability to hijack their hosts’ immune system is perhaps the most unique. O. unilateralis is not the only organism to cause similar behavioral manipulations of its hosts: the fungus Pandora formicae and the microscopic worm Dicrocoelium dendriticum have strikingly similar lifestyles.

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Luckily, no mechanism of fungal brain control has evolved to targeted humans (yet!). However, better understanding the means by which O. unilateralis can target particular ant species and tissues could have important implications for human health. Symptoms of some debilitating diseases, such as multiple sclerosis and cerebral palsy, involve damaged brain-neuron-muscle communication chains. It is not implausible to imagine that more fully characterizing how O. unilateralis uses particular secondary metabolites to chemically induce host movement might pave the way for new drugs that mitigate the symptoms of individuals with neuromuscular disorders. Improved mechanisms of targeted drug delivery to specific tissues could have far-reaching applications, from better directed anti-cancer treatments to common antibiotics.

Reference:

Fredericksen, M., Zhang, Y., Hazen, M., Loreto, R., Mangold, C., Chen, D. and Hughes, D. (2017). Three-dimensional visualization and a deep-learning model reveal complex fungal parasite networks in behaviorally manipulated ants. Proceedings of the National Academy of Sciences, 114(47), pp.12590-12595.