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Three episodes have been enough for half the world to be interested in mycology.

The fault lies with the HBO series

The Last of Us

, based on a game with the same name, and the fungus that in fiction has humanity on the brink of extinction,

Cordyceps

.

A real organism that has an innate ability to modify the behavior of its host, while devouring it from the inside

.

Paradoxically, these parasites are used as medicine, and their benefits are even being investigated to prevent rejection of transplanted organs.

To find out a bit more about what's scientifically real or plausible in the series and whether we should start to worry, we spoke with

David Hughes of Pennsylvania State University

, a Cordyceps specialist and science advisor on the 2013 video game;

and with

Javier Diéguez, scientific researcher at the CSIC

, PhD in mycology from the Upsala University, Sweden and associate professor at the University of California.

Cordyceps infection in humans is feasible, but...

In

The Last of Us

series , the Cordyceps fungus evolves, thanks to climate change, and manages to adapt and survive at 37 degrees Celsius in the human body, while currently it can't survive more than 32. "It could adapt, Of course. In fact,

it has already happened in the case of the fungus Candida Auris, which has recently adapted to the temperature of the human body,

"says Dieguez.

Although he explains that, in this case, the infection usually occurs in patients with severe burns or with some genetic immunosuppression.

In fact,

it is common in hospitals for a fungal infection to proliferate in patients with this profile

.

"As it is in the series, it could theoretically occur in the future, but it is an evolutionary scenario that requires millions of years.

The current Cordyceps have been selected in an evolutionary process of millions of years

," adds the doctor.

The rise in temperatures will make strains that have the ability to grow under these new conditions selected.

In addition, the increase in temperatures can also mean that there is not such a drastic change between the environmental temperature and that of the human body, an aspect that can be presented as an advantage for fungi.

Then, for these to adapt to humans, we would have to coexist for a long time, so that the more than 223 Ophiocordyceps species currently have the perfect adaptations to invertebrates, since their genome is adapted for these hosts.

"Infection is possible. In addition, parasites are a group of animals that jump to humans all the time, as Covid 19 did, although what I rule out is that they could modify our behavior

," explains Hughes.

Dispersal by bite, spores or food poisoning

In the game

The Last of U

s, people can become infected with Cordyceps through bites from the infected, as in the case of zombies in fiction, and by breathing in spores.

In the series,

the pattern of the bite is repeated and even at a specific moment, it is seen how an infected person passes the Cordyceps mycelium (a structure similar to a whitish root) to another person who is already infected

, but at a very early stage.

The first cases of infection are even linked to a flour factory.

What would be the method of spreading Cordyceps in humans?

"In the series they invent a new step, vampirism. The only stage in which insects bite, in the case of Cordyceps infection, is to anchor themselves in the spore dispersal zone.

They choose the most morbid of various species of mushrooms and put it in a

", says Diéguez.

Although theoretically, he adds, anything is possible, including dispersal by bite.

"There are many fungi that are spread by insects that bore holes in the plants and at the same time inoculate spores

," adds the expert.

As for food poisoning, the expert believes that the reference to the flour factory is used as an intermediate step in how Cordyceps passes from invertebrates to humans.

"When cereal, rice or wheat is harvested, insects or part of them are involuntarily collected, such as the cuticles (the wall of their exoskeleton) and the fungi attached to it," says Diéguez.

Although he adds that currently, this industrial process is highly controlled because it is known that toxins can appear.

Just as it happened with the epidemic of Saint Anthony's fire, or Ergotism, in medieval Europe, which was even documented by the painter El Bosco.

The culprit was rye flour contaminated by ergot, a parasitic fungus called Claviceps purpurea, which produces mycotoxins that cause hallucinations, vascular problems and even tissue necrosis in humans.

Apparently it was the reason for some cases of choreomania in which the infected danced until they dropped dead

.

In fact, Cordyceps itself secretes toxins, as a defense method, which are what modify the behavior of the insect.

Could a Cordyceps infection alter human behavior?

In fiction, in about 24 hours, the fungus is capable of colonizing a human being and altering their behavior, causing them to bite other people to spread the infection.

However, while Cordyceps does have the ability to alter the behavior of invertebrates, it doesn't work that way.

As detailed by Diéguez,

when the spore of this fungus reaches the cuticle of the insect, that is, the shell, it begins to germinate and hyphae are formed

.

Then they start to release degradative proteins, but not randomly.

They release them in a specific sequence that corresponds to the different layers of the insect's wall.

In addition, the hyphae have colonization structures called appressoria, which facilitate the fixation and penetration of a fungus in its host.

These own infection structures, chemically and physically super efficient, manage to 'drill' the exoskeleton of the insect and after colonizing

it, they can maintain a biotrophic growth, that is, they live in symbiosis until they find the right conditions.

It is then that they begin to degrade the insect, to devour it alive from the inside, as seen in the series.

During this process, the Cordyceps secretes toxins that alter the behavior of the insect at the will of the fungus.

This, evolutionarily, knows which proteins to secrete so that the ant, grasshopper or locust acquires a specific behavior.

So that it goes to a high area of ​​the plant or of the ecosystem, where it can better expand its spores with the wind.

It is in this phase, the reproductive one, when the fruiting bodies are produced, the mushrooms, which come out of the dead body of the insects towards the outside.

A phase that is recorded in the video game, but that has not yet been seen in the series.

So,

Cordyceps, in order to 'control' a human being, would need to adapt its genome to this new system.

, that is, to know and secrete the enzymes that, in the case of people, alter their brain chemistry, that is, their cognition.

Is there a cure for the infection?

Fungi are characterized by growing in tubular cells that have a cell wall.

When they infect, they create protection, hence the importance of addressing the phase prior to this shielding, just as occurs with bacteria and antibiotics, which are aimed at preventing this cell wall from being generated.

"In the series there is a key moment when they say that there is no possible drug or treatment. This is because

most antibiotics are designed for bacteria, which is our main problem, however, there are hardly any antifungals

," says Diéguez.

An immune person like Ellie would be doable

Despite the fact that, according to the CSIC scientist, the series is quite well documented, the issue of immunity represented in the character of Ellie is a somewhat more complex aspect.

There are two types of immunity, innate, which is what you are born with, and acquired, in which antibodies come into play.

In the case of vertebrates, such as mammals, acquired immunity learns to generate antibodies from exposure to pathogens.

However, insects do not have this system, they only have innate immunity.

When these are infected by Cordyceps, they secrete melanin, which has fungotoxic properties, which adheres to and blocks the hyphae and blackens them, thus killing the fungus.

Your immunity, and whether you survive exposure to the spores, will depend on how quickly you secrete this melanin.

The speed will depend on the populations, as it happens in humans, some are more resistant than others to certain diseases

.

It is true that this primitive mechanism is still preserved to protect us from the sun, however, when it comes to fighting a pathogen, acquired immunity is unparalleled.

For this reason, as Diéguez explains, it is perfectly possible that in

The Last of Us

a person has resistance or immunity to Cordyceps infection.

"It is the individual or the population, over time, that becomes more resistant to a pathogen"

, stresses the expert.

"When this happens, it is possible to know what are the molecular mechanisms that operate in this resistance and, in this way, develop a vaccine or a drug to treat the infection. Your blood serum will have antibodies or immune molecules, which can be studied to produce in mass and treat the population that is most sensitive to the fungus", adds the scientist.

Is such a rapid spread realistic?

In recent decades it has been found that the rate of disappearance of some animal species is very high and apparently, fungi seem to be partly to blame.

Globalization is causing any microorganism to jump from one place to another, thus finding the perfect host or simply new organisms to colonize.

"Devastating epidemics are taking place in plants and animals such as the sudden death of the oak, the drought of the Holm oak, the decrease in the survival of turtle hatchlings due to the fungus Fusarium solani, the massive deaths of corals, chytridiomycosis in amphibians or the plague of the crab", details Diéguez.

Authentic horror stories that are already happening in the animal kingdom, accelerated by globalization and climate change

, which makes many ecosystems vulnerable, due to the stress generated by temperature changes and the increasingly common extreme weather events.

So in the case of an infection like the one in the series, speed is guaranteed, as we already experienced during Covid-19.

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