In The Last of Us, humanity is devastated by a mutated Cordyceps fungus that infects humans, transforming them into aggressive, zombie-like hosts in a catastrophic pandemic. This gripping premise has captivated audiences of both the original video game series and its recent TV adaptation, sparking widespread curiosity about the plausibility of a fungal pandemic of this scale.
Upon the inception of the TV series in early 2023 google analytics revealed the searches “Could the last of us happen?” and “Cordyceps Fungus” spiked in popularity. In the wake of the COVID-19 pandemic this show has left many wondering: Could a worldwide fungal pandemic happen? And if it did, what would it look like?
The Real Cordyceps Fungus
The real-world inspiration for The Last of Us is Ophiocordyceps unilateralis, often called the zombie-ant fungus [1]. The Ophiocordyceps is a genus of fungi that is closely related to the genus Cordyceps, referenced in The Last of Us [2]. The zombie-ant fungus exhibits a fascinating example of an extended phenotype, where genetic influence extends beyond the organism’s physical traits to manipulate its host's behavior [3]. In this case, the fungus alters the ant's actions to fulfill its need for light, which is critical for its reproductive process [3]. Like a scene from a horror story, the fungus takes control of its host, compelling the ant to climb vegetation and anchor itself in prime spore-dispersal locations [3]. The infected ant's movements become erratic, marked by convulsions and isolation from the colony, culminating in the release of spores to propagate the fungus further.
The media attention on "zombie-ant fungi" and the premise of The Last of Us have amplified public concern, but experts assure that such a scenario is, at least for now, firmly in the realm of science fiction [1]. However, the growing prevalence of antifungal resistance and the potential for climate change to increase fungal infection rates underscore the need for vigilance and further research in this field.
Could a Fungal Pandemic Happen?
Fungal infections in humans are not new. Common conditions like athlete’s foot (tinea pedis) affect 15-25% of humans at any given time [4]. However, most fungi thrive at temperatures between 25°C and 30°C, while the human body’s core temperature of 37°C creates a natural barrier [5]. Unlike humans, ants are cold-blooded and they share an optimal temperature window with the majority of fungi, including the zombie-ant fungus. This allows for their susceptibility to infection. Yet, as global temperatures rise due to climate change, fungi may adapt to warmer conditions, potentially breaching this barrier and expanding their capacity to infect humans.
Compounding this concern is the limited arsenal of antifungal treatments. There are only three classes of antifungal drugs that are commonly used [6], and their effectiveness is threatened by growing fungal resistance, partly driven by agricultural misuse [7]. Unlike bacteria, fungi are eukaryotic organisms, making them biologically similar to human cells [8]. This similarity makes developing antifungals challenging, as treatments risk harming human tissues as well. Like bacteria, fungi are also prominent contributors to Antimicrobial Resistance (AMR). Bacteria have a high mutation rate, while the mutation rate of fungi is slower [8], it is still significant to create fungi strains that are resistant to all antifungals. The widespread use of antifungals for agriculture increases instances of fungi strains that are resistant to all antifungal treatments that can be used clinically.
What’s Next?
While The Last of Us is an enthralling exploration of survival in a fungal-apocalypse world, the science behind it—while rooted in real phenomena—stretches the boundaries of plausibility. The real Cordyceps fungus is fascinating and poses no threat to humans, but it serves as a stark reminder of how interconnected our world is and how environmental changes could shape the future of human health in unexpected ways.
There are actionable steps you can take to help mitigate the risk of rising fungal infections. Join local climate change initiatives to address environmental factors that enable fungal adaptation to warmer environments. Advocate for responsible use of agricultural antifungals by sharing your concerns with government representatives. Lastly, spark conversations with friends and community members to raise awareness and inspire collective action. Together, we can make a difference.
References
[1] Allyn B. The Last of Us: Is the zombie fungus real?. NPR. Published January 30, 2023. Available from: https://www.npr.org/2023/01/30/1151868673/the-last-of-us-cordyceps-zombie-fungus-real
[2] Sung GH, Hywel-Jones NL, Sung JM, Luangsa-Ard JJ, Shrestha B, Spatafora JW. Phylogenetic classification of Cordyceps and the clavicipitaceous fungi. Studies in Mycology. 2007;57(1):5–59. doi:10.3114/sim.2007.57.01. PMC2104736. PMID:18490993.
[3] Casadevall A, Kontoyiannis DP, Robert V. On the emergence of Candida auris: Climate change, azoles, swamps, and birds. mBio. 2019;10(4):e01397-19. doi:10.1128/mBio.01397-19. Available from: https://www.sciencedirect.com/science/article/pii/S175450481630112X
[4] de Bekker C, Quevillon LE, Smith PB, Fleming KR, Ghosh D, Patterson AD, et al. Species-specific ant brain manipulation by a specialized fungal parasite. BMC Evolutionary Biology. 2010;10:36.
doi:10.1186/1471-2148-10-36. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC2907807/
[5] Casadevall A, Kontoyiannis DP. Adaptation of fungal pathogens to host environments. Current Opinion in Microbiology. 2024;78:102008. doi:10.1016/j.mib.2024.102008. Available from: https://www.sciencedirect.com/science/article/pii/S1878614624000059
[6] Centers for Disease Control and Prevention (CDC). Fungal diseases: Clinical care guidelines for healthcare professionals. Available from: https://www.cdc.gov/fungal/hcp/clinical-care/index.html
[7] Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Chowdhary A, Gurr SJ, et al. Tackling the emerging threat of invasive fungal infections: A call to action. The Lancet Infectious Diseases. 2023;23(11):e345–e356. doi:10.1016/S1473-3099(23)00627-8. Available from: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00627-8/fulltext
[8] De Virgilio C, Loewith R. Cell growth control: Revisiting the concepts of growth and size. EMBO Reports. 2023;24(7):e57561. doi:10.15252/embr.202357561. Available from: https://www.embopress.org/doi/full/10.15252/embr.202357561
Image source: https://theconversation.com/the-fungus-zombies-in-the-last-of-us-are-fictional-but-real-fungi-can-infect-people-and-theyre-becoming-more-resistant-200224 Assessed and Endorsed by the MedReport Medical Review Board