Are Humans the New Target for Fungi? | Attack of the Zombie Fungus

**Sanitized Transcript:**

Deep in a jungle, a worker ant happily performs his task foraging food for his colony, oblivious to any danger. Only a minor irritation above: spores falling from a nearby fungus. One lands on his shell, a seasonal nuisance for a few days. Nothing changes, but then the ant begins to act erratically. It seems unable to control its own body. It leaves its colony alone, stops foraging, and its movements become increasingly erratic. It’s weakening but compelled to climb. In a final act, it bites down, fixing itself to its perch. Only then does its killer reveal itself: the thin, fleshy stalk bursts from the ant’s cranium. The fungus unleashes a new shower of spores into the air. At last, it has no more use for the ant and lets it expire.

The zombie ant fungus, properly named Ophiocordyceps, destroys entire colonies at a time. Ant corpses are left twisting in the breeze. Fungi have been around for at least 600 million years, and it’s estimated there are 1.5 million different species. Imagine this enormous group of organisms; they live by breaking down matter. When trees and leaves fall, fungi break them down. We think of them as nature’s recyclers, feeding on the dead leaves beneath our feet. It seems a peaceful, passive existence, but the soil they call home is a world teeming with life and one of the most competitive environments on Earth. To survive, they must fight off predators big and small: amoebas, bacteria, insects, and animals. This has made fungi super resilient, invincible, and potentially deadly.

You have all these strategies for surviving in the soil, but one of the fascinating things is that they learn to be pathogenic; they learn to cause disease. Most people worry about viruses and bacteria, but I am concerned about fungi and their capacity to do damage and destroy entire ecosystems. Fungi are killers and are more than ready to fight for their place on our planet.

The fungus that zombified the unfortunate ant, Ophiocordyceps, displays a starring role in the video game and television series “The Last of Us.” In the story, warming temperatures cause parasitic fungi to infect humans, turning them into brain-controlled zombies. Sixty percent of humanity is wiped out, and the remaining humans must constantly battle the infected. But that’s science fiction. So could it really happen?

In the real world, it’s not just ants; other species, including our own, are in a battle with parasitic fungi. Scientists have identified over 500 different types of Ophiocordyceps, and 35 of these have the ability to turn their hosts into zombies. When we use buzzwords like “zombie fungi” or “zombifying parasites,” we’re referring to the ability of the fungus or the interaction between the fungus and its insect host to produce novel behaviors that help the fungus transmit. Zombification means modifying a host rather than just killing it.

Each Ophiocordyceps species preys on one particular insect. The fungi zombify insect hosts like beetles, moths, crickets, and even spiders. The goal is the same: hijack a host, feed on it, and propagate. One species of Ophiocordyceps invades tarantulas by using long tubular cells known as hyphae. Once the tarantula’s insides are replaced by hyphae, the spider dies, and like with ants, a fungal stalk forms to release spores, spreading the fungus to its next victim.

For a parasitic fungus, the ultimate evolutionary goal is the continuation of the species and its populations. Another fungus, called Massospora, can infect cicadas and releases psychoactive compounds that cause the cicadas to behave differently and mate more frequently than they would otherwise. This causes the fungus to transmit from one cicada to another, widening its spread.

Inside forests, fungi grow in impressive formations. Bioluminescence makes some appear otherworldly. Fungi weave a network of thin tendrils known as mycelium below the forest floor. As part of their life cycle, fungi fruit by sending out stalks or pods like mushrooms. When ready, they release spores, reproductive cells that spread the fungus.

The first records of a mind-controlling fungus were made in 1859 by Alfred Russell Wallace, a great naturalist and contemporary of Darwin. He collected specimens in Indonesia and the Amazon to bring back to London, but sadly his specimens were lost when his ship caught fire and sank on the way home. Since then, scientists have tried to understand how a fungus controls an insect host so effectively.

Once an Ophiocordyceps spore attaches to the ant’s cuticle or exoskeleton, it generates a germ tube using enzymes and brute force to eat through the cuticle. The long tube drops into the hemocoel, the ant’s body cavity, which is full of hemolymph, their blood equivalent. The fungus can infiltrate that space and produce what we call blastospores, which are single-celled versions of the fungus. As they divide, the blastospores break down the ant’s tissue into sugars and feed on them.

After a couple of weeks, you’ll start to see some breakdown in the ant’s behavior, such as tremors and convulsions. Most of the ant’s muscles are ravaged, but the ones that control the mandibles are left intact. This lets the ant clamp onto a branch or leaf before dying. It’s still a mystery how a group of fungal cells coordinates to the extent that they dictate a creature’s behavior.

Scientists have a few hypotheses about the mechanisms involved. One theory is that fungal cells get inside a host’s brain and take over all motor functions. Others believe that zombifying fungus cells don’t enter the brain but surround it, forming a kind of halo. This suggests that one of the key mechanisms of fungal interference with host behavior is keeping the brain intact while influencing it through secreted chemicals or proteins that interfere with neurons. The fungus may mimic neurotransmitters like serotonin and dopamine, affecting the ant’s nervous system.

The ants do fight back; they are social insects that groom each other, much like chimpanzees do, by routinely checking each other for spores. This reduces the chances of a fungus invading their bodies. A fungus is driven to infect at any cost. It’s no surprise when one decimates an entire species. This happened with the mystery of the dwindling frogs, first noticed in the rainforests of Central and South America and Australia. Huge populations of frogs were turning up dead from heart attacks. The killer was an aquatic fungus called chytrid, which causes a skin disease in amphibians that leads to cardiac arrest. Amphibians are helpless against chytrid because it paralyzes their immune cell response. Ninety amphibian species around the world have gone extinct because of this one fungus.

Parasitic fungi also attack mammals, especially those with cooler body temperatures. A previously unknown fungus has been slaughtering millions of bats in the U.S., causing a disease known as white-nose syndrome, named for the fuzzy growth on their muzzles and wings. The cold-loving fungus was discovered in 2007 deep inside caves. Biologists in upstate New York noticed hibernating bats behaving strangely. The fungal infection was causing them to wake up frequently, making them use up their fat reserves and starve before spring could arrive. Over 90% of bat colonies in North America have died from white-nose syndrome.

Scientists worry that someday some unknown fungi could make the jump from diseased animals to humans. They’ve done it before. We don’t have very good information on fungal diseases of animals because they’re not studied. We’re not looking at a major fungal threat like we do with viruses. Just as there’s a battle between fungi and animal bodies, there’s a battle between pathogenic fungi and our bodies.

You can’t see the fungus; what you’re seeing is the evidence of its presence through tissue damage. In the case of athlete’s foot, you get a lesion on the toes; in the case of a nail infection, you get a discolored nail. Fungi cause other minor discomforts like jock itch, thrush, and yeast infections, all of which can be treated with a trip to the pharmacy. However, some can cause severe health problems on a mass scale. Each year, 1.5 million human deaths are due to diseases caused by parasitic fungi, which is more than four times the number of deaths from malaria.

In “The Last of Us,” one of the main characters is a young teen born with a rare immunity to the zombie fungus. If she’s bitten by one of the infected humans, her body is able to contain it. In real life, our immune system does an impressive job of protecting against fungal invasion. Our immune cells consist of macrophages, which is Greek for “large eaters.” These big patrol cells are everywhere in our body; they ingest and break down fungal cells, eliminating them.

However, if one becomes immunosuppressed, those macrophages don’t work as well, and that’s when fungal diseases occur. Immunosuppressed means a person with a weakened immune system. These are patients undergoing chemotherapy for cancer, transplant recipients taking drugs to prevent organ rejection, and people living with HIV or AIDS, who run an especially high risk for fungal infection. This often occurs during a hospital stay.

Ten to 20 million people around the globe have weakened immune systems, and that number is growing. In recent years, fungal infections have increased in frequency around the globe. There have also been increased cases of fungal diseases following COVID-19 or severe COVID. This is due to how the COVID-19 virus interacts with a person’s immune system. The virus destroys tissue inside the lung, allowing opportunistic fungi to settle in. In India, COVID-19 led to a surge in cases of a potentially fatal infection by a fungus known as black fungus, which caused a rare infection called mucormycosis. This infection blocks blood flow, killing infected tissue and causing a black discoloration on people’s skin. Left untreated, it is fatal.

Black fungus lives in soil, decomposing vegetation, and animal dung. When people get near any kind of fungus, they may inhale its spores. Humans take an average of 23,000 breaths per day, and each breath can contain from 1 to 10 fungal spores. People could be inhaling a huge amount of potentially lethal spores every day, and our interactions with fungi are only just beginning.

In the fictional world of “The Last of Us,” warming temperatures due to climate change caused the fungus to mutate and infect people. There was no way to stop it. In the real world, climate change may not spur parasitic fungi to conquer humanity anytime soon, but a warming climate may spur them to crop up in more places around the world. During hurricanes, flooding damage can cause increased growth of fungi and molds that can then cause infections and diseases, including asthma. Scientists are already seeing an uptick in fungal diseases, and even more disturbing is that many are appearing for the first time in the American Southwest.

There’s a fungus called Coccidioides found in the dirt, and when it’s disturbed, it can aerosolize and be breathed in by people. Coccidioides causes a disease known as valley fever, first noticed among farm workers in California’s Central Valley. Workers who inhale spores from the soil develop respiratory symptoms like a cough or chest pain. Most recover, but in some cases, valley fever becomes a chronic infection that leaves abscesses in the lungs and can eventually lead to death.

As the climate warms and droughts become more frequent, there’s an increased risk of Coccidioides entering the air through dust or disturbance of the dirt. A disease modeling study predicts that by the year 2100, the range for valley fever fungus will expand as far as Kansas and North Dakota. But it’s novel fungal infections that are the most concerning. Parasitic infections in people are rare because most fungi, like Ophiocordyceps, live in cooler temperatures. However, as the climate has warmed, most fungi have adapted to higher temperatures, like those found inside a warm human body.

This is what happens in “The Last of Us.” If fungi can grow in more bodies, this could spell trouble for the planet. The world is getting warmer, and the question is: what’s going to happen to fungal diseases? This brings us to Candida auris. Candida auris was not known to medicine prior to 2007. It is the first example of a fungal disease emerging out of the climate crisis. The first case occurred in Tokyo, then in 2011, Candida auris appeared simultaneously on three continents: Asia, Africa, and South America.

Some researchers propose that what happened was that Candida auris adapted to higher temperatures and thus was able to defeat our temperature defenses, emerging as a human pathogenic fungus. A current wave of Candida auris outbreaks has made news headlines, growing from only a dozen cases a few years ago to over 2,000 today. When the fungus enters the bloodstream, it causes a blood disease called invasive candidiasis. Like the zombie fungus in the ant, Candida auris consumes the tissue of its host, attacking internal organs, genitals, the mouth, eyes, and skin.

The Centers for Disease Control estimates that up to 70% of patients infected with Candida auris have died. Other factors make Candida auris a dire global threat. It’s difficult to detect using standard laboratory methods; screening requires sophisticated equipment that most hospitals can’t afford. The fungus is often misidentified, leading to the wrong kind of treatment. By the time the mistake is corrected, it may be too late. Once it settles in a healthcare facility, an outbreak is almost impossible to contain.

A hospital in London had to completely shut down in 2016 because its Intensive Care Unit couldn’t get rid of the fungus. In October 2022, the World Health Organization put Candida auris on its list of global health threats. Scientists around the world are searching for ways to stop it, hoping that what they learn can be applied to tackling another deadly fungus on the list: Cryptococcus neoformans.

A lot of people are exposed to Cryptococcus neoformans on a day-to-day basis, especially those living in cities, because it’s quite common in pigeon guano. The fungus enters through the respiratory system and can lead to cryptococcal pneumonia. If it spreads to the central nervous system, it can cause life-threatening cryptococcal meningitis, which is a brain infection. It causes increased intracranial pressure, affecting mood and behavior. Victims often become erratic, lethargic, and super sensitive to light.

This is the closest humans get to experiencing the effects of a mind-controlling zombie fungus. So far, Cryptococcus neoformans shares something else with the zombie fungus: it also treats a host body as food. If it gets within a host cell, it needs a lot of nutrients to divide and grow. It can take some nutrients from within the host for its own benefit and can be a stealthy killer. After infecting a person, Cryptococcus spores can hide inside human immune cells, waiting for the right moment.

In some people, the immune system manages to wall off the infection, creating a little area that is isolated, where the fungus can survive for many years. Some people then take drugs that make them immunosuppressed, and when they do, that little wall can break down, allowing the fungus to come out and unleash a severe fungal infection when conditions become favorable for unrestricted growth, such as when a person’s immune system weakens.

So if fungi are adapting to a warming world and feeding on our bodies, how can we stop them? In “The Last of Us,” scientists hope the immune girl may provide some kind of cure for the deadly infection. In the real world, scientists don’t fully understand why certain fungi activate an immune response while others don’t. Cryptococcus neoformans has distinct features that could provide an explanation. A layer of carbohydrates surrounds each fungal cell, called the polysaccharide capsule. Other fungi don’t have this.

This polysaccharide is slimy, making it very hard for immune cells to hold on to the fungus and eat it. It creates problems for how the immune system can function. The polysaccharide capsule also acts like an invisibility cloak, making it harder for immune cells to track down and kill a Cryptococcus cell. This may be because fungal and human cells share the same basic structure, making targeting just a fungal cell with a drug difficult. Treatments that are toxic to fungi are just as toxic to humans.

What about a vaccine? This is what some of the survivors in “The Last of Us” are hoping for. The immune girl’s brain cells may be the key component. Is it possible to have a fungal vaccine against fungal diseases? Absolutely, in the laboratory, we can make them. The problem is not in the science; the problem is in developing them. Many of these vaccines, even though their efficacy can be demonstrated in the laboratory, fail to be developed further since the cost of development is enormous.

This hasn’t stopped scientists from trying. Fungal vaccines could be major game changers for immunosuppressed people living in areas without medical care. Ever since the COVID-19 pandemic began, scientists have been concerned that a tenacious fungus could trigger a new pandemic. There is no reason why a fungal pathogen can’t cause an epidemic. We don’t have historical experience of a fungal epidemic, like the Black Death or COVID, but just because it hasn’t happened doesn’t mean it can’t happen.

If a new epidemic were to start, there’s no guarantee it could be quickly contained. Currently, there are only a handful of drugs that treat deadly fungal diseases, each targeting a different fungus. Given the multitude of species, creating enough effective drugs may be next to impossible. Another problem is that fungi can develop resistance to medication in the same way bacteria develop resistance to antibiotics.

We need to be on guard; these organisms are dangerous. I am worried about them and their capacity to do damage and destroy entire ecosystems. The resilience of fungi is one of their most disturbing qualities. They’ve evolved to survive the most hazardous conditions. For example, in 2008, a fungus was discovered growing inside the Chernobyl nuclear plant, where an explosion caused a Soviet nuclear reactor to almost melt down in 1986.

When researchers went there a few decades later, they found that the walls of the area were coated with a black fungus. This is an area where if you and I walk into, we would receive lethal radiation in a few minutes. While researchers were intrigued by what was going on, they discovered that the fungus was capturing high-energy radiation and using it to grow, similar to how plants capture sunlight for photosynthesis.

Fungi are so indomitable that they can even survive in space, like growing inside the International Space Station. Black mold was found in places where astronauts had hung up their workout clothes to dry. The spores had come with the air supply from Earth. Once in orbit, the mold withstood prolonged doses of space radiation, 200 times higher than what would kill a human. If fungi can endure space travel, they could spread to other parts of the solar system.

That’s why NASA and space agencies are very careful about what they send out there, as they may contaminate other worlds. If fungi can