Why Diseases Caused by Fungi Are So Frightening

Fungi are having a cultural moment, thanks in large part to the horror franchise The Last of Us, in which society has collapsed after an outbreak of a fungal infection that turns humans into violent, zombie-like hosts. While real-life fungi won’t be turning us into zombies any time soon, they have become an increasingly worrisome threat to our health. Fungal infections are a lot harder to treat that those caused by bacteria. Here’s why.

When fungi invade the body

Fungi don’t make us sick very often, outside of typically minor ailments like athlete’s foot or a vaginal yeast infection. Most fungi like to live in moderate temperatures, with their optimal range hovering around 70 to 80 degrees Fahrenheit—notably below the roughly 98 degrees of our internal body, says Arturo Casadevall, a molecular microbiologist at Johns Hopkins University who specializes in fungal infections. While we do naturally carry some fungi inside us, their numbers are drastically smaller than our bacterial tenants, and harmful fungal infections rarely take root.

Casadevall and many other scientists were inspired to study these infections in the wake of the HIV/AIDS epidemic. Before the advent of antiretroviral therapy, HIV infections would routinely devastate people’s immune systems, leading to outbreaks of fungal disease almost never seen before. Thankfully, with timely treatment, these AIDS-related fungal infections are now a rarity in places like the U.S. But people in general are becoming a more appealing host for fungi these days, for other reasons. Modern medical advances have allowed us to extend lives with donated organs and to treat once incurable cancers. But these advances often require the use of medications that suppress the immune system, at least temporarily. That weakening can provide just enough of an opening for some fungi to cause a serious infection. And because fungal infections are more likely to happen in people with compromised immune systems, they’re usually an inherently harder challenge for doctors to treat than a routine ear infection or a case of strep throat caused by bacteria.

“When bacteria get into the body, they can cause disease even in small numbers. Whereas with fungi, they’ll kill you slowly, and since they kill you slowly, they often multiply to have lots of organisms before you even begin treatment. So one problem is that you have a lot more fungal organisms around,” Casadevall told Gizmodo. “And then the antifungals don’t work as well as the antibiotics, because these drugs will cooperate with the immune system. But often in these cases, the immune system isn’t working. So you got multiple things going on at once, and that’s why, when you hear about somebody having an invasive fungal infection, it’s often been going on for a long time.”

Fungi are also harder to fend off once they become trouble, because we simply have fewer tools available to stop them. There are four major classes of antifungals, with only 10 drugs approved by the FDA to treat systemic fungal infections, compared to the eight major classes and hundreds of antibiotics available for bacteria. Antifungals tend to be less effective, at least in part due to our relatively close similarity to fungi.

“Fungi are eukaryotic [organisms whose cells contain a membrane-bound nucleus], like us, but bacteria are prokaryotic. So that’s why it can be challenging to find drugs that can hurt them but not be too toxic to us,” Mahmoud Ghannoum, professor of dermatology at Case Western Reserve University, told Gizmodo.

“Adapt or die”

Unfortunately, much like bacteria, fungi are evolving resistance against the few drugs we have against them. Ghannoum and other researchers have been documenting the emergence of ringworm fungi that are starting to resist front-line antifungals, for instance, including strains that are spreading sexually. Other fungi are becoming more heat-tolerant, in no small part thanks to climate change. The fear is that some of these heat-adapted fungi will start to infect people more regularly—a fear that may have already come true with the arrival of Candida auris.

C. auris was only discovered in 2009 and is now considered one of the more serious and worsening infectious disease threats. The fungus can routinely resist several antifungals at once and spread quickly in vulnerable locations like hospitals and nursing care facilities. Casadevall and other scientists have found evidence that C. auris is the first—but perhaps not the last—fungal infection to have emerged from climate change. Climate change can also shift environmental conditions to expand the range and survivability of certain fungi. Some research has suggested that this has already happened with the fungi that cause Valley fever, which has historically been confined to the Southwestern U.S. but is now showing up in other states.

“It’s a simple argument: Everything in the world has to either adapt or die. And the fungi, when they adapt—we’re not going to be able to keep them out with our temperature any longer,” said Casadevall, who recently co-authored the book What If Fungi Win?, which looks at how fungi are poised to further threaten not only our health but our crops and other ecosystems.

But there is hope on the horizon. Both Casadevall and Ghannoum note that researchers are working on developing new antifungals and vaccines to the most worrying fungal pathogens. Scientists elsewhere are trying to refine immunosuppressant therapy to lessen the risk of opportunistic infections, to reduce or even eliminate the use of such drugs for organ transplants, and to boost people’s immunity directly to better fight off fungal infections.

As scary as fungi are now and could become in the future, humanity is certainly working to adapt right back.