by Clio Morata de Jong and Nico Morales
Following a long tradition of submissions from undergraduate students, this piece was written as part of an assignment for the Microbial Pathogenesis course taught by Prof. Cheryl Okumura at Occidental College. All of us at STC are very grateful for Cheryl's continued support. –Roberto
In the realm of natural mind control, few phenomena are as gripping—literally—as the death grip of the parasitic fungus in the genus Ophiocordyceps. As described in a previous STC blog post, this fungus doesn’t just kill its carpenter ant hosts; it transforms them into instruments of fungal propagation, culminating in one of the most macabre spectacles in the natural world. Infected ants are driven by the fungus to climb vegetation and lock their mandibles onto twigs or leaves in an ironclad bite, ensuring they remain perched high above the forest floor. From this vantage point, the fungus grows and releases spores, sending infectious particles down to the unsuspecting ants below. If this premise feels ripped from science fiction, that's no coincidence – HBO’s hit series The Last of Us opens with a grim warning about fungi such as Ophiocordyceps evolving to infect humans. While such a leap is purely fictional (for now), the real-life manipulations of Ophiocordyceps are equally chilling, especially because this parasitism affects the most populous species on the planet. Because of the elaborate manipulation needed to achieve fungal spread, the relationship between Ophiocordyceps and their hosts remains a subject of investigation.
Figure 1: In situ photographs showing the infection of Ophiocordyceps unilateralis sensulato on eight different sympatric ant species. Photo credit
Early research suggested a strict one-to-one specialization between fungal strains and ant species. For example, a 2011 paper using traditional micromorphology techniques demonstrated that Ophiocordyceps could be clearly separated into distinct taxa that infected unique ant species, leading to the "one ant, one species" hypothesis. In fact, the authors stated that differences in fungal morphology and ant ecology were "so pronounced that molecular characterization is not required to separate them." Given the vast species diversity of Ophiocordyceps and their hosts, these data suggest a high level of specialization for each fungal species to adapt to invading and exploiting a single ant species. However, such a strategy could be an evolutionary "dead end" and poses an interesting problem where the fungal ancestor must undergo specialization many times. Recent research conducted by Wei-Jiun Lin and colleagues has revealed surprising findings about the fungus – a single species complex, in this case O. unilateralis, could infect at least eight different ant species (Figure 1). Phylogenetic analyses revealed no cryptic genetic differences among the fungal samples found in different ant species despite morphological differences. This discovery suggests that O. unilateralis may rely on universally effective mechanisms rather than species specialization, which requires genetic adaptations such as developing unique enzymes or mechanisms to bypass host immune defenses. However, the authors found that this is not without its flaws, as a more generalist strategy resulted in reproductive fitness tradeoffs in alternate host species.
Building on this broader debate about host specificity, recent research has also explored the precise mechanisms by whichOphiocordyceps manipulates its hosts, shedding light on the physiological processes that enable its control over ant behavior. In 2019, Mangold et al. investigated the mechanics behind the "zombie ant" phenomenon. Ophiocordyceps colonizes the mandibular muscles, ensuring the ant remains fixed to vegetation while the fungus completes its life cycle. Despite extensive damage, the motor neurons and neuromuscular junctions remain intact, allowing fine-tuned fungal control. The multiterminal nature of insect muscles, where each fiber is innervated by multiple motor neurons, may further facilitate fungal control. This neuromuscular architecture provides multiple access points for fungal interference, potentially explaining why Ophiocordyceps evolved such a universal strategy. Hypercontraction of the muscles drives the death grip even as structural degradation occurs, facilitated by fungal hyphae that invade muscle fibers (Figure 2), degrade tissues enzymatically, and form dense networks. This invasion breaks down Z-lines, causing sarcomeres to shorten and fray into a locked state. Additionally, fungal compromise of the sarcolemma may allow direct injection of molecular signals, overriding the ant's natural signaling pathways. It is hypothesized that this injection of fungal molecules is done through the release of extracellular vesicles, visualized in the mandibular space. The exact contents of these vesicles remain unknown, but it appears likely that they include bioactive molecules that interfere with normal cellular signaling.
Figure 2. Ophiocordyceps inserts hyphal projections into host muscle. Photo credit
These studies not only highlight how Ophiocordyceps transforms ants into tools for its survival but showcase an evolutionary tradeoff between generalism and specialization. The paper by Wei-Jiun Lin and colleagues poses the problem of the "parasite paradox" – how do highly specialized parasites shift to novel hosts? We may need to consider expanding our scope of investigation – do ecological or environmental factors such as habitat or social dynamics play a role? Indeed, Lin et al propose that conflicting observations in their work may reflect differences of population dynamics of ant hosts among different forests. Another STC blog post reminds us that the relationship is made more complex by the presence of the hyperparasitic fungus Clavicipitaceae.
Further research on Ophiocordyceps could have applications in pest management, biodiversity conservation, and even human medicine. Fungal extracellular vesicles (EVs), which may influence host physiology, could inspire precision drug delivery systems, while insights into muscle hypercontraction mechanisms have potential applications for treating human disorders. Far from the pitch decks of writers' rooms, Ophiocordyceps reminds us that however wild science fiction gets, it is still based in the creativity of science itself.
Clio Morata de Jong will graduate from Occidental College in May 2025 with a degree in Biology. She works in Occidental's Marine Ecology Lab with Dr. Amber Stubler studying the effect of urchin predation on sponge boring rates. She is an avid sci-fi consumer – one of her favorite shows, The Last of Us, inspired her to write this blog post.
Nico Morales will graduate from Occidental College in May 2025 with a degree in Biology. On top of his studies, he competes for the Occidental Track and Field team in Javelin and works in the Biology Stockroom.
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