Could the Zombie Fungus in TV’s The Last of Us Really Infect People?

In the fictional world of The Last of Us, a fungus has destroyed the world. The new hit TV show highlights Ophiocordyceps unilateralis, an actual “zombie ant” fungus, which compels an infected insect to climb onto a leaf, lay down and wait for spores to sprout from its head and into the wind.

The show takes place in the wreckage of a pandemic, when a mutant strain of the zombifying fungus makes the leap to humans. That jump is no small feat because most species of fungi cannot survive the high temperatures of a warm-blooded body. “It’s far-fetched,” says Tom Chiller, chief of the Mycotic Diseases Branch at the Centers for Disease Control and Prevention. “That’s just not going to happen.”

But even if microbes don’t hijack our body and sprout from our head, newly infectious and drug-resistant fungi are an emerging to threaten human health. Scientific American spoke with Chiller about this fictional pandemic to understand the real possibility of a major fungal outbreak and how our changing climate may worsen these threats.

[An edited transcript of the interview follows.]

The series centers around a species of Ophiocordyceps fungus that really exists. Can you separate the fact from fiction for us?

There is zero correlation with that fungus in humans. This “zombie ant” fungus really does infect ants. But no Ophiocordyceps species invades any fish, amphibians or mammals. Insects are a much more rudimentary system. They have a much lower body temperature, a much simpler set of internal organs. It probably took millions of years for this fungus to develop to infect in an ant, and I imagine it would take millions of years for it to even begin to develop in a human.

Now clearly, some fungi have developed the ability to survive at our high body temperature. And maybe because people are warming the climate, other fungi are becoming more adaptable to these higher temperatures and could more easily make the jump into our body. But for Ophiocordyceps, there’s no chance.

We’re all familiar with bacterial and viral pandemics. Why don’t we see fungal pandemics? Is it just our high body temperature?

It’s probably more nuanced. We’re dealing with a complex kingdom of organisms. Fungi are much more self-sustainable, unlike a lot of viruses or bacteria. Fungi don’t usually need to infect to live. The good news on the human side is that generally fungi aren’t passed human-to-human. Now, some are, and some more appear to be developing that ability. And if we are seeing fungi that are more contagious, more infectious, more drug-resistant, then certainly we’re going to be concerned about larger infection events like epidemics and pandemics.

[Read our feature story about multiple reasons why new fungal diseases are emerging and already kill 1.6 million people every year]

I’ve heard a lot about outbreaks of the fungus Candida auris in health care settings. Is that one of those emerging fungal diseases?

That’s one that really came out of nowhere. We first heard about it in 2009, described in a Japanese patient. Then a hospital in London had to shut down because they couldn’t get it out of their ICU. It was transmitting from patient to a bed, back up to another patient. All these really nasty, drug-resistant bacteria that we see in hospitals—C. auris is acting like that. We still don’t know exactly why it emerged. It’s in more than 50 countries now, and in more than half of the U.S. It’s spreading, and it’s probably here to stay.

You mentioned that the changing climate could play a role in pressuring these fungi to survive in new places. That’s one of the implied causes of the pandemic in The Last of Us. How often do we see this in real life?

Most fungi that we deal with are in the environment, and they are highly sensitive to environmental changes. Any warming, cooling or changes in general, fungi are going to be affected by them.

Could they adapt to infect new kinds of hosts?

There’s no question. We see this now. We saw it with C. auris in humans. And there’s the fungal white-nose syndrome that’s wiping out hibernating bats in the U.S. I know that we’re going to see more of these fungi move into humans and into animals. We need to be constantly doing surveillance to understand how these things emerge.

How prepared are we to handle a large-scale fungal outbreak?

We’re going to be very challenged. Number one, we don’t have great diagnostics in this field. That really needs to be expanded to focus on fungi, as well as bacteria and viruses. Then the second area is treatment. We are severely limited. We really only have three classes of drugs to treat severe invasive fungal infections. We know that some C. auris are resistant to all three of those classes. What are we left with then? The good news is there are drugs in the pipeline for the first time in decades, but we need a lot more.

I’ve read that there are no vaccines for any fungal infections. Why?

People have tried and just not been successful. And there really hasn’t been much interest or investment at all from the big pharmaceutical companies. I think we do need government and other entities to step in and say, “Alright, we need to invest in these.”

That being said, we have a couple of interesting vaccines out there that are much closer than they’ve ever been. And I think the whole field of vaccinology has really moved forward. Certainly COVID has helped drive that. So I’m actually cautiously optimistic that we will see, potentially, a couple of human vaccines for Candida and [the fungus Coccidioides, which causes] valley fever, in the next few years.

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