The year is 2003, and a species of Cordyceps fungus has made the leap from ants to humans, transforming its hosts into frenzied, bloodthirsty zombies that spread the infection to everyone they bite. The solution proposed by a leading mycologist in Jakarta, Indonesia, where the first cases were detected, is radical, but in her view, essential: bomb the entire city and everyone in it to stop the infection in its tracks. Last month, HBO’s long-awaited post-apocalyptic series The Last of Us hit our screens, to huge acclaim from both critics and fans. It posits that it isn’t viruses or bacteria that pose the greatest threat to society, but fungi – those same organisms beloved by brewers, bakers and wild-food enthusiasts. More specifically, climate change has prompted Ophiocordyceps unilateralis, commonly known as “zombie-ant fungus”, to adapt to surviving at higher temperatures, rendering humans an alternative host. The writer-producer Craig Mazin – who also gave us the Chernobyl miniseries – has defended the show’s premise, explaining that everything it suggests fungi do, they already do, and have been doing forever – including hijacking ants’ brains and compelling them to propagate their killers’ spores. Other fungi can already produce mind-altering effects in humans (think magic mushrooms). The Last of Us is still very much science fiction, but there are plenty of other reasons to worry about fungi. Already, fungal infections kill about 2 million people each year – more than either TB or malaria – and the number is growing. Fungi are also becoming increasingly resistant to the small number of treatments available, and there are very few alternatives in the pipeline. The world was relatively unprepared for a viral pandemic when Covid hit, but at least scientists were already developing coronavirus vaccines. There are no human vaccines against fungi. In October, the World Health Organization released its fungal priority pathogens list, the first global effort to create a mycological “most wanted” list of the 19 fungi most dangerous to humans . “Despite posing a growing threat to human health, fungal infections receive very little attention and resources globally,” the report said. “This all makes it impossible to estimate the exact burden of fungal infections, and consequently difficult to galvanise policy and programmatic action.” Fungi are the most populous life form on the planet, with an estimated 12 million species existing worldwide. Most have never been categorised. Only a fraction of these species infect humans, but they are responsible for roughly a billion infections each year. “Most of those are superficial things like athlete’s foot, that no one’s particularly bothered about, but there is a core group that causes life-threatening infections, and particularly in susceptible populations such as the very old or young, and those with immune systems that don’t work properly,” says Mark Ramsdale, an associate professor of mycology at the MRC Centre for Medical Mycology in Exeter. About 1.5 million people die a year as a result of these infections, says Ramsdale – although that may be an underestimation, because fungi predominantly infect people who already have major health problems. “The primary cause of death will probably be leukaemia or heart transplant, or whatever,” he says. “But the thing that actually kills the patient is a fungal infection, so there is a strong element of underreporting going on.” Topping the WHO’s list are three forms of pathogenic yeast, plus Aspergillus fumigatus, a common mould found in soil and decaying vegetation which can cause a life-threatening infection called Aspergillosis in people with compromised immunity, such as those with HIV, chronic lung disease, or organ transplant recipients. Some of the fungi on the WHO list can affect healthy people as well. Coccidioides, known colloquially as “Cocci”, are soil-dwelling fungi found in the south-western US, Mexico, and parts of South America that cause a flu-like illness called Valley fever in a subset of people who breathe them in. Up to 10% of infected individuals will develop serious or long-term lung problems, while in about 1% of cases the infection spreads to other parts of the body, including the brain, where it can prove fatal. Roughly 150,000 people in the US are infected each year, and about 75 die from it. The range of some of these infections is also increasing. Cases of Valley fever have recently been detected as far north as Washington state. The number of reported infections also increased 400% between 1998 and 2015, possibly due to climate change. Other fungal infections appear to have increased as a result of Covid, including aspergillosis and mucormycosis, or “black fungus syndrome”, a rare but dangerous infectionthat can cause infected tissue to die and turn black. Because these infections are more common in people with suppressed immunity or lung damage, doctors suspect they are capitalising on the physical damage wreaked by Covid. The symptoms of mucormycosis can be gruesome. Often starting in the sinuses, the infection may spread to neighbouring tissues and organs, including the eyes and brain, resulting in blackened skin, facial swelling, blurred vision, altered consciousness or coma. Some patients have lost vision in both eyes, or had to have surgery to remove dead or infected bone and tissue. Horrible as these diseases are, one saving grace is that most fungal diseases aren’t transmitted from person to person. Rather, they are usually picked up from the environment, which tends to limit their spread. Mucormycosis, for example, is 70 to 80 times more prevalent in India than in the rest of the world. However, there are exceptions to this rule. One is Candida auris, a deadly relative of the yeast that causes thrush. It is on the WHO’s “critical” list as it is rapidly outpacing our best antifungal treatments. Like many fungal pathogens, Candida auris predominantly preys on people with weakened immune systems; if it gets into their blood, or invades other organs and tissues, their chances of survival are roughly 50-50. Similar to the fungus in The Last of Us, Candida auris came at us from out of the blue. It was unknown to science until it was found in the ear canal of a 70-year-old Japanese woman in Tokyo in 2009. Within a couple of years, infections had been reported across Asia, Africa and the Middle East. “It is now all over the world, and is an absolute nightmare in hospitals because it is resistant to a lot of the frontline antifungal drugs,” says Prof Matthew Fisher from the MRC Centre for Global Infectious Disease Analysis at Imperial College London. It is also partially resistant to disinfectants and heat, which makes it extremely difficult to eradicate. Its detection can trigger the temporary closure of entire hospital wards. Where Candida auris came from is uncertain. “We’re guessing that in the deep fungal biodiversity that is out there, this particular species got lucky,” says Fisher. Certain factors may have contributed. Climate change may have promoted the shift of this organism from an unknown host to us, and it’s even possible that, as in The Last of Us, warmer temperatures have selected for variants that can grow at human body temperature. Another possibility is that the overuse of antifungal drugs in medicine or agriculture has suppressed the growth of competitor organisms, opening up niches in which drug-resistant strains of Candida auris, and other potentially harmful fungi, can thrive. Compounding the problem, only four classes of antifungal drugs exist, and there are very few in the pipeline. Developing new drugs will be challenging. “Because fungi are actually quite closely related to animals, any drugs that can interfere with a fungus’ growth and development are quite often toxic to us,” Ramsdale says. Despite these concerns, fungi currently receive less than 1.5% of all infectious disease research funding. The WHO report calls for increased surveillance and antifungal development, as well as better diagnostic tools, to ensure patients are promptly treated with the correct drugs. Education is also critical, says Ramsdale: “Many medics receive only one or two lectures [on fungal pathogens] during their entire training at medical school.” The WHO said it was important not to sensationalise the threat posed by fungi. Antibiotic-resistant bacteria present a more immediate and quantifiable threat. “This is a call to increase awareness, to generate evidence, and to generate science – not just the research and development of new products, but also the basic science to understand the disease dynamics, epidemiology, ecology, and global distribution of fungal infections,” says Dr Hatim Sati, of the WHO’s antimicrobial resistance division, who helped write the report. Yet, the threat posed by fungi isn’t necessarily confined to species that have evolved the ability to infect us. About 6,000 species of fungi are known to cause disease in commercial plants, and each year 40% of the world’s rice crops are lost to a fungal disease called rice blast disease. “That’s a huge food security issue,” Ramsdale says. The WHO’s report also does not deal with unknown fungal threats – ones that have not yet made the leap to humans. Since the 1990s, conservation biologists have watched in horror as species after species of amphibian has succumbed to a disease caused by chytrid fungi which has been linked to the decline of at least 500 amphibian species, and the extinction of 90. Similar to the imagined scenario in The Last of Us, there is no known effective measure for controlling the disease. With so many fungal species out there, watching out for emerging threats is a daunting task. “There aren’t enough mycologists in the world to keep track of all of this,” Ramsdale says. Training more of them would be a good place to start. But as much as fungi present a danger to us, they also present opportunities. The world’s first antibiotic, penicillin, was discovered in a mould. Who knows what other chemical tricks they have up their mycelia? “Like bacteria or viruses, fungi are ancient, and they are everywhere,” says Fisher. Underestimating them would be a mistake.