These Tiny Creatures Are Wiping Out Species Across the Globe. They’re Coming for Humans Next.

Here’s what you’ll learn when you read this story:

• Because of a warming planet and changing human physiology, fungi are learning how to infect humans more effectively. Meanwhile, agricultural overuse of antifungal drugs may be helping fungi evolve resistance before they ever infect humans.
• A deadly yeast, Candida auris, has emerged independently on multiple continents within just a few years. This fungal species can survive for weeks on dry surfaces and, once it enters the bloodstream, can colonize organs including the liver, lungs, and heart and be fatal in up to 60 percent of patients.
• But there’s hope: Researchers are getting creative with new ways to shore up our immune defenses against the fungal invader.

For 17 years, Arturo Casadevall has watched an evolutionary crisis of his own forecasting unfold in slow motion across the globe.

Driven by a warming planet and shifting human physiology, the fungal kingdom—home to yeasts and molds—is breaching our species’ biological defenses. Cases of deadly fungal infections are surging, and modern medicine is woefully ill-equipped to stop them.

“Humanity is not prepared for a fungal pandemic,” warns Casadevall, MD, PhD, who is chair of molecular microbiology and immunology at Johns Hopkins University. We are on perilous terrain, he says, and asleep at the wheel.

The warning signs began in 2009, when an unassuming yeast was isolated from the ear canal of a patient in Japan. It arrived already armed with resistance to one of our three primary classes of antifungal drugs.

“Nobody thinks anything of it at first, because you report new fungal diseases every year,” Casadevall explains. “But what was amazing was what happened over the next few years: Candida auris (named for the Latin word for ear) emerged simultaneously as a human pathogen across South America, South Africa, and the Indian subcontinent. And the isolates were completely unrelated.” Unconnected strains soon surfaced in Iran, Russia, and Singapore. Today, the Centers for Disease Control and Prevention (CDC) ranks Candida auris as an “urgent threat”—its highest alert level for a microbe.

The clinical portrait of a Candida auris infection reads like a medical thriller. It doesn’t confine itself to the ear. It can persist for weeks on all surfaces, including dry hospital furniture, and if it hitches a ride on an intravenous catheter, it quickly slips into the bloodstream. Once inside, it colonizes internal organs, coating the liver, lungs, and heart. The body attempts to mount a defense, but in up to 60 percent of invasive cases, the host’s immune system fails to contain it, leading to death.

According to Casadevall, what is driving this global rise in fungal pathogen spread is that the difference between the temperatures of mammals and the temperatures of their ambient environments has been narrowing. Most fungi thrive in cooler environments, and for millennia humans have been protected by a biological “thermal shield”—our internal body heat is simply too warm for most fungal species to replicate. But a warming climate is forcing environmental fungi to adapt to higher heat, suddenly making the human body a far more hospitable environment.

This thermal convergence is further compounded by a quiet physiological shift: Modern human bodies are getting cooler. Studies have found that thanks to cleaner living environments, widespread hygiene, and modern medicine, our immune systems face less chronic inflammation than our ancestors did, resulting in a measurable drop in baseline human body temperature over the last century.

Ana Traven, PhD, a professor of medical mycology at Monash University in Melbourne, stresses that public awareness and research investment lag dangerously behind the evolving fungal threat. But her primary concern isn’t just climate change—it is our alarming lack of medical defenses. Unlike bacterial infections, for which doctors can choose from dozens of antibiotic classes, modern medicine relies on a meager three major classes of antifungals to treat invasive diseases. To make matters worse, fungal resistance against this thin line of defense is climbing fast, leaving clinicians with dangerously few options when treatments fail.

“Overspraying crops is 100% the problem,” Traven says. “We are spraying crops and using the same classes of drugs that we use in the clinic on these crops.” Industrial agriculture routinely douses fields with triazoles to protect food supplies from crop rot. This practice creates environmental pressure that selects for resistant fungal mutations long before the fungi ever encounter a human patient. As a result, emerging environmental yeasts enter hospital intensive care units already armed against our frontline drugs.

Designing effective antifungal therapeutics is an exceptionally tough evolutionary nut to crack. Unlike bacteria, which are prokaryotes with vastly different cell structures, fungi are eukaryotes—meaning they share our complex cellular architecture and biochemical pathways.

“With bacteria, you have a better chance to kill the bacterium without killing the human,” Traven says. “With fungi, the cell biology, the biochemistry, everything is conserved. So it’s really hard to find targets that you can hit that would be fungal-specific.”

To bypass the challenge of finding fungus-specific drug targets, Traven turned her focus to the human immune system. Her team discovered that when Candida yeasts invade, they outcompete host immune cells for sugar, triggering a metabolic stress response that activates NINJ1, a macrophage-rupturing protein. These immune cells—which fight fungi by engulfing them whole—burst under elevated levels of NINJ1, allowing the fungus to break free from the host immune defenses and spread through tissue. Traven’s team determined that administering the amino acid alanine to the host blocks this NINJ1-driven rupture.

While promising, Traven stresses that this strategy is nowhere near enough. One major issue is that the field of medical mycology remains far too small globally. To solve complex fungal threats, science needs a “critical mass” of researchers approaching the problem from diverse, creative angles, because “you never know where the big breakthrough is going to come from.”

As deadly as Candida auris is, it lacks the machinery to spark a true global pandemic—its reach remains largely confined to direct contact among the most vulnerable, particularly the elderly and immunocompromised. But Casadevall warns that a far more contagious pathogen could eventually emerge.

“How would it work? You need a fungus to be airborne,” Casadevall says. “And it can happen if the fungus sporulates in the lung and you cough it up.”

For anyone who believes an airborne fungal pandemic feels comfortably remote, Casadevall offers a sobering reality check. “They say—go ask the Spartans. I say—go ask the frogs, which have lost 100 species already in the greatest cataclysm that has happened to amphibians,” he says. “Frogs have been killed the world over in a fungal pandemic. Bats have been killed in North America. Salamanders in Europe are being killed right now.”

The fungal kingdom has already proven its capacity for destroying species; humanity’s only choice is whether we wake up before we become its next target.