Maybe you’ve heard of Cordyceps before, that fascinating and horrifying group of fungal parasites known for invading the bodies and brains of tropical ants and turning them into zombies who march helplessly into the forest understory, dying with their jaws clamped down in a death grip on the nearest plant. Perhaps you’ve seen this BBC Planet Earth clip and watched in horror as the fruiting body of the fungus erupted from the host’s head, ready to rain down deadly spores on the hapless insects below. If so, did you ever wonder how the fungus manages to accomplish its incredible (and terrifying) feat of control – hijacking the body and the nervous system of an organism from another kingdom in order to carry out its own biological imperative and enhance its reproductive success? Have you ever wondered about the evolutionary pressures that led to such a (disgustingly) intimate and profound relationship between parasite and host? You did? Well then you, my friend, are my kind of person – and you should read on because I’ve got a paper here that delves into some of those very questions.

Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection

Hughes DP, Andersen SB, Hywel-Jones NL, Himaman W, Billen J, Boomsma JJ. BMC Ecology. 2011 May 9;11(1):13. doi: 10.1186/1472-6785-11-13.

Before we get going though, let’s have a quick review of our star parasite here. Cordyceps are a group of obligately parasitic fungi which parasitize ants and other insects, primarily in tropical areas. In this paper the researchers looked specifically at Ophiocordyceps unilateralis, a species which infests the ant Camponotus leonardi, in Thailand. There are hundreds of species in the Cordyceps genus however, and they all share a striking life history that is famously straight out of a ’50s science fiction B movie.

When Cordyceps spores land on an unfortunate host organism, they take root within the body of their victim. The growing mycelium (the network of fungal threads that makes up the main body of most fungi) gradually infiltrates the host’s tissue, harvesting the host’s body for nutrients and eventually killing it. When the fungus finishes consuming the body of its host from the inside out (leaving the hapless insect literally just an exoskeletal shell of its former self) its spore body bursts forth from within and spreads its spores over whatever other potential hosts may be living in the area.

Some Cordyceps, including O. unilateralis, take this process a step further. In addition to invading the bodies of their hosts, they also are capable of invading their minds. Cordyceps like O. unilateralis don’t just destroy their hosts’ tissue, but in fact are capable of repurposing the nervous and musculoskeletal systems of their hosts to change their behavior. Ants infected with O. unilateralis don’t just die horribly – instead, just before they die horribly, their fungal parasites induce them to climb out onto a leaf and clamp their jaws onto the veins of the plant they are standing on in a “death grip” which ensures that even in death they will remain poised above the forest floor, where the spores of their fungal nemesis can more effectively rain down upon those below.

How does this happen? This degree of manipulation of the host seems practically unbelievable, coming from a species as “simple” as a fungus. Obviously such fine control could only be the product of a longstanding coevolutionary relationship between fungal parasites and insect hosts. (Coevolutionary relationships are relationships in which the evolution of one species is shaped by the evolution of another, and vice versa.) What, though, are the mechanisms by which Cordyceps does its ghastly work?

Hughes et al 2011

Well, that’s what this paper tries to get at. The above image depicts a magnified cross-section of a C. leonardi head taken from a living (at the time of sampling) ant found in the “death grip” pose, and it hints at some of the authors’ discoveries – fungal mycelium (inset, top left) embedded within the nervous system tissue of the ant, and atrophied muscle (inset, bottom right) in its mandibles. Before I go further though, let’s see that abstract:

Parasites that manipulate host behavior can provide prominent examples of extended phenotypes: parasite genomes controlling host behavior. Here we focus on one of the most dramatic examples of behavioral manipulation, the death grip of ants infected by Ophiocordyceps fungi. We studied the interaction between O. unilateralis s.l. and its host ant Camponotus leonardi in a Thai rainforest, where infected ants descend from their canopy nests down to understory vegetation to bite into abaxial leaf veins before dying. Host mortality is concentrated in patches (graveyards) where ants die on sapling leaves ca. 25 cm above the soil surface where conditions for parasite development are optimal. Here we address whether the sequence of ant behaviors leading to the final death grip can also be interpreted as parasite adaptations and describe some of the morphological changes inside the heads of infected workers that mediate the expression of the death grip phenotype.

I’m going to ignore that “extended phenotype” business for the time being, as the concept is one of those annoying Richard Dawkins metaphors which, while not totally without merit, is a bit over-reaching and an example of how science-reporter sensationalism can be perpetrated even by those who call themselves serious scientists. (See also the “selfish gene” concept. Don’t even get me started.) Instead I want to focus on what I think is really interesting about this paper, which is its insight into the mechanisms by which parasites can manipulate and repurpose the bodies and behaviors of their hosts in order to serve their own reproductive ends.

Here’s a bit more from the paper:

We found that infected ants behave as zombies and display predictable stereotypical behaviors of random rather than directional walking, and of repeated convulsions that make them fall down and thus precludes [sic] returning to the canopy. Transitions from erratic wandering to death grips on a leaf vein were abrupt and synchronized around solar noon. We show that the mandibles of ants penetrate deeply into vein tissue and that this is accompanied by extensive atrophy of the mandibular muscles. This lock-jaw means the ant will remain attached to the leaf after death. We further present histological data to show that a high density of single celled stages of the parasite within the head capsule of dying ants are likely to be responsible for this muscular atrophy.

Pretty amazing stuff happening there if you ask me. What gets me is that not only does the Cordyceps manage to effect the locomotion of its host – causing it to wander erratically and fall down, thus helping to ensure that it ends up at the right height for the fungus’s purposes – and not only does it induce its host to clamp down on a leaf in order to anchor itself in place, but it also manages to synchronize the latter behavior to solar noon. Here’s a graph for that:

Hughes et al 2011

The yellow bars here are solar elevation, while the red dots are the times at which ants bit down on the leaves in preparation for death and transformation into fungal spore factories. Pretty neat, yeah? I think so anyway. The authors unfortunately don’t speculate too heavily about the possible mechanisms behind this phenomenon (anybody out there feel like writing that research proposal?) but they do talk more about the mechanism by which the O. unilateralis to maintain its “death grip” on the plant substrate:

At the moment of the death grip, when the ant is under fungal control and biting into the major vein of a leaf its head is filled with fungal cells (Figure 3 [See top of post – Ed]). These cells, called hyphal bodies, were very abundant and could be found between the muscle fibers and surrounding the brain and post pharyngeal gland (Figure 3), but not inside muscles, brains or glands.

The most prominent other sign of infection, besides the abundance of fungal cells inside the head capsule, was that the mandibular muscles were atrophied. We sectioned the heads of 10 ants that were biting leaves and the pathology was the same across all 10. Mandibular muscle fibers, which normally attach to the head capsule, often appeared to have become detached (Figure 3c) and where fibers remained attached they were stretched (compare 3b and 3c). Ant workers have both mandibular opening and closing muscles and these can be discriminated in healthy ants by their typical length of sarcomeres: 2-3 µm for opening muscles and 5-6 µm for closing muscles (Figure 3b). However, in parasitized ants the characteristic stretching of sarcomeres made it impossible to accurately distinguish between these two types of muscles. This may imply that fungal effects on these muscles are unlikely to be cell specific at the time of biting. Our behavioral observations revealed that the mandibles worked normally in the hours preceding the death grip as infected ants were observed to self groom, cleaning their antennae and legs, which involves precise opening and closing of the mandibles as these appendages are pulled across the maxillae to be cleaned.

Figure 3, which is displayed at the top of this post, clearly shows the invasion of the ant’s head capsule by fungal mycelium and the atrophy of its mandibular muscles. It would seem that in order to prevent the ant from letting go once it has anchored itself to a leaf, the fungus destroys the muscles which would ordinarily open the ant’s jaws. Pretty hairy stuff, that. The authors have kindly included a photo of leaf damage caused by ant death grips, which it is my pleasure to pass on to you:

The authors close with several questions. They would like to know more about the mechanism by which the fungus destroys the ant’s jaw muscles. They would like to know how the fungus manages to synchronize the biting behavior to solar noon. They also observed that zombie ants are usually found in a North-North-West orientation – but nothing is known about why this should be so. In fact, there are a whole host of unknowns in the weird and grisly world of zombie ants:

While our behavioral observations support an extended phenotype explanation serving the Ophiocordyceps interests, they do not explain why infected ants occur on leaves of a distinct NNW orientation or how the fungus causes its hosts to choose distinct parts of the leaf. Although ants were apparently manipulated into biting a wide range of plant species including both monocots and dicots (Figure 5), the location of the bites on main leaf veins remained highly invariant, with 98% of ants attaching to a major primary or secondary vein. Our present work showed that the mandibles directly enter the vein of the leaf that is bitten (Figure 5) and the transition from walking to biting is abrupt and happens in a matter of minutes (ca. 20 h of observations following 16 zombie ants). Only in a few cases did the ants rasp the leaf or bite multiple times leading to multiple scars (Figure 5a). Our data does not explain why bites are centered on major veins or indeed what cues are used in deciding between lamina and vein. We suggest that the local topology (veins are raised above the lamina) provide a stimulus to biting behavior.

Fertile ground for more study, I suppose. Personally I could read about Cordyceps all day, but I’d much rather hear what y’all think. In the meantime, I’ll just be over here, watching that Planet Earth clip over and over again.