Could the zombie fungus in The Last of Us really infect humans?

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

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

But even if microbes don’t hijack our bodies and sprout from our heads, newly infectious and drug-resistant fungi are an increasing threat to human health. Scientific American spoke to Chiller about this fictional pandemic to understand the real possibility of a large fungal outbreak and how our changing climate could exacerbate these threats.

[An edited transcript of the interview follows.]

The series revolves around an Ophiocordyceps species of mushroom that actually exists. Can you separate fact from fiction for us?

There is no correlation with this fungus in humans. This “zombie ant” fungus actually infects ants. But no Ophiocordyceps species invades 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 this fungus millions of years to evolve to infect an ant, and I imagine it would take millions of years for it to even evolve in a human.

Now, some fungi have clearly evolved the ability to survive our high body temperatures. And perhaps as humans warm the climate, other fungi will become more adaptable to these higher temperatures and could make the leap into our bodies more easily. But for Ophiocordyceps there is no chance.

We all know bacterial and viral pandemics. Why aren’t we seeing fungal pandemics? Is it just our high body temperature?

It’s probably more nuanced. We are dealing with a complex realm of organisms. Unlike many viruses or bacteria, fungi are much more self-perpetuating. Fungi don’t usually need to become infected to survive. The good news on the human side is that fungi are not generally passed from person to person. Now some are, and some seem to be developing that ability. And when we see fungi that are more contagious, more infectious, and more drug-resistant, then we’ll certainly worry about major infectious 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 healthcare settings. Is this one of those emerging fungal diseases?

This is 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 close because they couldn’t get it out of their intensive care unit. It was transmitted from one patient to a bed and back to another patient. All those really nasty, drug-resistant bacteria that we see in hospitals — this is how C. auris behaves. We still don’t know exactly why it arose. It is now available in more than 50 countries and in more than half of the United States. It will probably stay.

They mentioned that climate change might play a role in putting pressure on these fungi to survive in new places. This is one of the implied causes of the pandemic in The Last of Us. How often do we see this in real life?

Most of the fungi we deal with are found in the environment and are very sensitive to environmental changes. Any warming, cooling or change in general, mushrooms will be affected.

Could they adapt to infect new types of hosts?

No question. We see that now. We have seen it in C. auris in humans. And there’s fungal white-nose syndrome, which is wiping out wintering bats in the US. I know we’ll see more of these fungi spread to humans and animals. We need constant monitoring to understand how these things are formed.

How well are we prepared for a large-scale fungal infestation?

We will be very challenged. Number one, we don’t have great diagnostics in this area. This really needs to be expanded to focus on fungi as well as bacteria and viruses. Then the second area is the treatment. We are severely restricted. 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 these classes. Then what are we left with? The good news is that drugs are in the pipeline for the first time in decades, but we need a lot more.

I read that there are no vaccines against fungal infections. Why?

People have tried and just haven’t been successful. And there really hasn’t been much interest or investment from big pharma. I think we need governments and other bodies to step in and say, ‘okay, we need to invest in these.’

That being said, we have a couple of interesting vaccines out there that are a lot closer than we’ve ever been. And I think the whole field of vaccinology has really evolved. COVID has certainly helped drive this forward. So I’m cautiously optimistic that we might see some human vaccines for candida and candida [the fungus Coccidioides, which causes] Valley fever, in the next few years.