The Cordyceps fungus can turn its host into a zombie and cause its death, but not quite like in the series; the genus contains species with medicinal properties.

Although fictional, the story of the series "The Last of Us" (HBO Max) is not entirely removed from reality: the Cordyceps fungus genus, which in the plot almost decimates humanity, actually exists. The difference is that in real life, this fungus can infect ants, caterpillars, and other insects, not humans. This alone excludes the danger - at least for now - of humanity suffering a lethal zombie fungus pandemic.

"There is no knowledge of Cordyceps fungus species capable of surviving in the human body and causing death in the way seen in the series. Fungi can mutate, but we do not know if a pandemic caused by a fungal infection can happen someday, but it seems to me a very remote possibility," explains Ana Olívia de Souza, a postdoctoral researcher in biochemistry from the Faculty of Medicine of Ribeirão Preto, who studies the pharmacological application of substances produced by different species of fungi.

In the dystopian reality of the series, the Cordyceps fungus mutates and infects humans, who become zombies capable of infecting others with each bite. In nature, there are over 400 species of fungi in the Cordyceps genus alone; of these, Ophiocordyceps unilateralis is the one that behaves most similarly to the one in the series - but in insects.

"This fungus actually turns the ant into a zombie because it secretes neurotoxins inside the animal, which then compromise the functioning of the insect's muscles, changing its behavior in the ant colony. After being infected, the ant becomes disoriented and begins to look for brighter places, eventually leaving the ant colony. In this process, it spreads the fungus spores that have already taken over its body," explains Tainah Colombo Gomes, a biotechnologist from Ana Olívia's team.

The infection by the fungus - which lasts from 2 to 5 days - turns the ant's body completely whitish, resembling mold. Full of microscopic spores inside and out, the ant's limbs begin to be paralyzed by the action of neurotoxins. Unable to move, the ant dies, and the remains of its inert body continue to be useful as food for the fungus. This reproductive process of Ophiocordyceps unilateralis has ensured its survival, says Rafael Conrado, a senior technician at the Laboratory for Development and Innovation (LDI).

"This fungus makes the ant have a very specific behavior: when it leaves the ant colony, it attaches itself to a nearby plant and, once attached, the fruiting body grows on its head, which is the fungus's reproductive organ. It is where Cordyceps releases its spores, which can infect other ants right there, be deposited in the soil, or be carried by the wind or insects to other places," Rafael describes.

As in fiction, a twist can happen and change the sad fate of the members of this ant colony. When they notice an infected animal, the colony tries to prevent mass infection.

"In the ant colony, the workers perceive the strange behavior of the ants acting like zombies and then remove them from the colony so that they do not come into contact with the others. They are not rational like us, but they manage to eliminate the infected ants to protect the others," says the LDI researcher.

The zombie fungus

Ophiocordyceps unilateralis, also known as the "zombie fungus," was discovered by British naturalist Alfred Russel Wallace in 1859 and is predominantly found in tropical forests, such as the Amazon. It infects carpenter ants (Camponotus cruentatus) that feed on fungi and live in hot and humid locations, environments that facilitate its proliferation.

This relationship between O. unilateralis fungus and the ant is the result of a long process of evolution, indicating that the insect carries the necessary conditions for the fungus to survive.

"Over the years, the fungus has adapted to the ant's organism, whose body temperature is different from that of humans, and whose nervous system is much less complex. In the beginning, perhaps there was a beneficial relationship between the ant and the fungus, which would have helped in this process. To develop in a human body, the fungus would have to undergo many adaptations and still find a body with a severely weakened immune system," explains LDI doctoral student Luiz Gustavo Ribeiro.

Cordyceps Fungi and Chinese Medicine

Other species of Cordyceps fungi have beneficial qualities, including for human health - such as Cordyceps cicadae, Cordyceps sinensis, and Cordyceps militaris, widely used by traditional Chinese medicine.

"The three species are described as producers of compounds with different pharmacological properties: anti-inflammatory, antitumor, immunomodulatory, nephroprotective, and hepatoprotective. The beneficial Cordyceps fungi have been considered a rare commodity in China," says Ana Olivia.

It is not new to science to use the beneficial side of microorganisms as a source of medicines and other products. A great example is penicillin, discovered from a fungus, which became an excellent antibiotic used for decades. "In our laboratory, our research aims to find a molecule that has pharmaceutical applications," explains the researcher.

One of LDI's research lines includes a study that addresses the healing and antimicrobial action of molecules produced by fungi. The goal is to use them in different products, including a cream for wound healing and/or an antibiotic product.

"In our research, fungi are also used for the development of nanomaterials that can have pharmaceutical applications and to combat fungi harmful to grain production in agriculture," concludes Ana Olivia."

Zombie Fungus and Medicinal Cordyceps: Discover the Fascinating Relationship between Ophiocordyceps Unilateralis and Camponotus Cruentatus Ants, and the Healing Properties of Cordyceps Fungi in Traditional Chinese Medicine