The hit HBO series ‘The Last of Us’ has been adapted from a popular video game of the same name. In the game and the show, a deadly fungal outbreak causes humans to turn into zombies as the infection takes control of the hosts’ minds and makes them look like very scary mushroomy people. While the story and the mushroom zombies are fictional, the fungus that infects them is very much real! Yes, Cordyceps are real and they are a species of parasitic fungus but before you have a panic attack about the mushroom risotto you had last night, you should know that they only infect insects. So unless you’re an ant, you need not get all antsy because there is nothing to worry about.

There are over 700 types of Cordyceps sp. and various species tend to attack different kinds of insects like spiders, caterpillars, and moths but the show drew inspiration from Ophiocordyceps unilateralis, also known as the zombie-ant fungus. Infection initiates when an insect encounters the asexual spores, known as conidia, which germinate on its surface. Secretion of hydrolytic enzymes such as chitinases and lipases facilitates successful infection, while protective enzymes like peroxidases shield the spores from UV radiation. The spores then start growing a short germ tube which penetrates the insect and then the fungus starts infecting internal organs and effectively enslaves the host. The ultimate objective is to release additional spores and infect more insects.

Some of the zombie-like behaviors of the infected people in the show resemble the actual behavior of infected insects in the real world. Cordyceps-infected ants have been observed to wander around and stray away from their colonies similar to the wandering around of the infected mushroom zombies. This behaviour serves the fungus by distancing the ant from its colony before suspicion arises. Likewise, the show depicts a protocol for killing suspected infected individuals, mirroring how healthy ants attack and eliminate infected ants.  It also manipulates the ant to move to elevated positions like on top of a tree where the wind and other environmental conditions might favour the spreading of these spores. On arrival at the desired location, Ophiocordyceps-infected ants bite the plant hard and then their jaws get locked in this ‘death grip’ and then the ant dies. The fungus then devours it and sprouts out through its head. This description almost sounds similar to the later stages of the infected, or ‘clickers’ as they called them on the show who have not very delicious-looking mushroom heads. These mycelia that are grown out from the ants head, then burst open and release more spores perpetuating the cycle.

In “The Last of Us,” cordyceps infects the brain, yet in reality, studies reveal Ophiocordyceps doesn’t enter the ant’s brain. Instead, it controls movement through mechanical and chemical processes, causing tissue destruction or changes in internal pressure. For example, the death grip bite is a result of the destruction of the membrane of the muscle fibers in the jaw which results in contractions strong enough to damage the muscle filaments that slide past each other when the muscles contract. This basically means that the ant is a prisoner in its own body and has to serve a master – who despite his name, does not sound like a fun guy!

After hearing these horror stories, one might ponder the outcome if humans were infected by cordyceps. Fortunately, due to stark differences between humans and insects, cordyceps cannot invade us. Experts suggest the likelihood of such mutations is improbable in the future. Even if we encounter the spores, our high body temperatures and robust immune systems would thwart fungal survival. In the show, this evolved fungus spreads to humans through infected crops, but in reality, you can literally add cordyceps to your breakfast! Long used as supplements, they are speculated to offer potential health benefits, including anti-inflammatory, anti-diabetic, anti-aging, and even anti-cancer effects.

Global warming aids cordyceps to evolve to adapt to human body temperatures in ‘The Last of Us’ echoing real-life concerns. While cordyceps evolving to infect humans remains unlikely, climate change is a risk factor for boosting the thermal tolerance of other fungal pathogens. The similarities between a human and a fungal cell also make it hard to develop new anti-fungal drugs that will not harm our cells in the process and drug resistance has always been a concern. So in the extremely unlikely event that cordyceps do miraculously evolve to infect humans, we’re all gonna be mushroom toast!

Reference (Feb-24-A2)














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