Zombie Fungus from “The Last of Us” Spurs Increased Interest in Fungal Research

Zombie fungus. 

It is one of the top searches on Google this year thanks to the popularity of the hit HBO show “The Last of Us.” It also has people reaching out to scientists at the Environmental Molecular Sciences Laboratory (EMSL) to see if it is possible for a fungus to cause a zombie apocalypse. 

In the show, a type of real fungus called Ophiocordyceps unilateralis (also known as zombie ant fungus) has evolved to withstand higher temperatures due to global warming. As a result, it survives invading the bodies of humans, overtaking internal systems (including the brain) to effectively render its hosts zombies. 

In today’s reality, the fungus predominantly compromises insects like ants, which have far simpler nervous and immune systems, said Scott Baker, a fungal biologist and leader of the Functional and Systems Biology science area at EMSL. Baker also has a joint appointment as a fungal biotechnology scientist with Department of Energy's Joint BioEnergy Institute.

“It’s realistic that this fungus could evolve to survive higher temperatures in the future, but it is unlikely that it will evolve to impact humans as is portrayed on the show,” he said. “If it did evolve to withstand higher temperatures, it might make some people sick, especially those who are immunocompromised, but not to the level that you see on the show.” 

Baker has spent a significant portion of his career characterizing and studying genetic components of different fungi and how to apply them to a variety of industrial and agricultural applications. He is a fan of “The Last of Us”—both the show and the original video game it is based on. His son has played through the game, and the two are now enjoying the show. 

And even though the show and game are not entirely accurate about the probable future of the Ophiocordyceps unilateralis fungus, Baker said they portray some important technical components about the fungal world. For example, the show accurately portrays the real ability of fungi to operate as an extensive network, he said. It also dives into the enormous complexity of fungal lifestyle modes, which are very diverse, he said. 

Baker said the popularity of the show has led to an increased interest in fungi as a whole, which presents a great opportunity to shed light on how fungi are being used to solve global challenges. Among the fungi-related research, EMSL staff scientists and EMSL users are breaking down hardy plant materials for bioproducts production and for plastics degradation, and are even analyzing how a type of fungi is thriving in a highly radioactive environment at the Chernobyl nuclear disaster zone. 

“Fungi are having a moment right now,” Baker said. “Does the show cast a negative light on a particular type of fungus? Yeah, sure. But I think it’s also helping to shed light on some of the good stuff. There are a lot of cool projects about fungi happening right here at EMSL.” 

Degrading hardy plant material for bioproducts production 

Several EMSL staff scientists and EMSL users are studying how to use fungi to degrade hard-to-break-down materials for developing bioproducts and reducing waste products. 

Davinia Salvachúa, a research scientist at the National Renewable Energy Laboratory and an EMSL user, is accessing EMSL via a Large-Scale Research proposal to study white rot fungi. Specifically, she is studying how these fungi break down a compound called lignin, which is a primary component in the cell walls of plants that makes them sturdy and rigid. She is also studying how these organisms use lignin breakdown products as a food source. The material is incredibly hard to break down, she said. Today, a good portion of the material is disposed of as a waste product or even burned, contributing to harmful greenhouse gas emissions. 

“White rot fungi are the only known organisms that efficiently break down lignin,” she said. “Our focus is on identifying fungal pathways and enzymes involved in the subsequent conversion of lignin degradation products.” 

Salvachúa said after lignin is broken down, resulting carbon can be used to make biofuel precursors and other important bioproducts. 

“You can turn what would be a waste product into a valuable compound using more sustainable alternatives for its production compared to the petrochemical industry,” she said. 

Like Salvachúa, Michelle O’Malley, a professor of biological engineering and chemical engineering at the University of California Santa Barbara and an EMSL user, is studying fungi as a means to break down lignin. But instead of examining white rot fungi, she is looking at a type of fungi found in the guts of herbivores like cows, sheep, and goats. It is a type of fungi that is anaerobic, or one that doesn’t need oxygen to survive. 

O’Malley has a project with the Facilities Integrating Collaborations for User Science (FICUS) program, which allows her and her team to partner with EMSL and other Department of Energy user facilities to access a range of scientific instruments and expertise for her research. 

“We look at the proteins and metabolic pathways that these fungi make and try to build better technologies inspired by these fungi,” she said. 

O’Malley’s project seeks the use of EMSL and Joint Genome Institute resources to determine the structure of unique, multi-enzyme cellulosomes made by anaerobic gut fungi. Cellulosomes, she said, enable the synergistic breakdown of plant biomass into fermentable sugars. 

She said the fungus cellulosomes present promising biotechnology tools to drive lignocellulose conversion—or turning lignin into a usable bioproduct. With the project, the team aims to reveal critical attributes of fungal cellulosomes that can be engineered and exploited for lignocellulose breakdown and bio-based fuel and chemical production. 

Using fungi to reduce plastic waste 

Among a variety of other projects, Kevin Solomon, an assistant professor of chemical and biomolecular engineering from the University of Delaware and an EMSL user, is studying how to use fungi as a means to bind together and degrade microplastics. 

Recent work in his lab isolated a novel fungal strain that creates a strong and adhesive biofilm that quickly scavenges and accumulates microplastics in a diluted environment. As part of a limited-scope project through EMSL, he and his team are using spatial proteomics, mass spectrometry imaging, and X-ray computed tomography to generate a chemo-physical model of plastics binding. The model will help inform how microbial plastic accumulation occurs, as well as strategies to improve microbial access to microplastics for enhanced degradation and upcycling. 

As part of a project through the FICUS program, Solomon is also a member of a team led by Mark Blenner, an associate professor of chemical and biomolecular engineering from the University of Delaware, studying how organisms present in the guts of insect larvae can be used to degrade plastics. He said insect microbial communities degrade plastics rapidly compared to singular microbes and simple consortia. 

“If you look at different environments, some organisms are better at breaking down materials than others,” he said. “Insects, such as yellow mealworms, which are the larvae stage of the [mealworm] beetle, have shown success degrading microplastics stemming from materials such as polystyrene and polyethylene.” 

Polystyrene is used for a variety of insulation materials. Polyethylene is the most common type of consumer plastic in the world. It is used in materials such as packaging film, grocery and trash bags, in toys, in cable and wire insulation, and many others. Solomon said because it is used everywhere, its waste is seen everywhere, which is difficult to degrade. 

“With our projects, we are trying to understand how different microbes and enzymes secreted in mealworm gut microbiomes degrade plastics,” he said. “One of the focuses is on bacteria. However, we are also paying attention to fungi to understand how they support the process.” 

Ants more than just hosts of zombie fungus 

Ants are typically the reality-based example of insects most affected by the fungus portrayed in “The Last of Us.” But a species of ant is also an excellent example for how an insect is using plants in their environment to grow a fungus as a food source and to fend off harmful types of fungus. 

Kristin Burnum-Johnson, a biomedical scientist at EMSL, is studying how leaf cutter ants use leaves gathered from the rainforest environment to grow a type of fungus, Leucoagaricus gongylophorus, that they consume as a food source. This fungus has applications in degrading plant-based materials for the creation of a variety of bioproducts like biofuels, she said, because it is excellent at degrading lignocellulose. 

Her team is also studying how the ant’s fungal garden ecosystem can fight off types of pathogenic fungus. In collaboration with team member Margaret Thairu, a postdoctoral researcher at the University of Wisconsin-Madison, they are studying how this ecosystem has the ability to adapt and produce antifungal molecules, which keep pathogenic species at bay. 

“We need to study fungus because if all hell breaks loose and there are zombies, understanding how natural ecosystems protect themselves can help us identify future antifungals,” she said jokingly. 

But in all seriousness, she said antifungals are key to fending off fungi that are not helpful in the world—those that cause health detriments in humans and animals, and those that destroy crops. 

Thriving fungus at Chernobyl sheds insights into biosensor development 

Erin Bredeweg, a fungal biologist and geneticist at EMSL, does a lot of work on the genetics and cellular components of fungus. While many of her projects pertain to the eventual scale up and development of bioproducts and materials, she is also working with Brian Clowers, an associate professor of chemistry and mass spectrometry chemist at Washington State University, on a project studying radiotrophic fungal species found at the Chernobyl nuclear disaster site. These fungi may be radiotrophic, which is a concept where organisms can break down ionizing radiation into a usable energy form. 

“This fungi produce melanized molecules that seem to be protective and allow them to use the energy from radiation in order to grow,” Bredeweg said. 

Fungal melanins, similar to how melanin in skin helps protect the body from harmful ultraviolet rays, help protect against chemical and physical environmental stressors, she said. 

The team is looking at two different types of melanized fungi: Exophiala dermatitidis and Cladosporium sphaerospermum. The latter type of fungus has been found as a pathogen on citrus plants. 

“We are studying how the fungus responds to stressors by looking at the differences in melanization pathways,” Bredeweg said. “This information can be used to develop a biosensor for radiation. If we determine a radiation-specific response pathway, we can use synthetic tools to develop strains that become more melanized or have a visual read out when they are exposed to radiation.” 

Hear Baker and Salvachúa talk about fungal research on EMSL's podcast, Bonding Over Science.