The basics
How fungi survive the drugs meant to kill them.
Most antifungal drugs work the same basic way: they jam one tiny machine the fungus needs to stay alive. A fungus becomes resistant when it finds a way around that. There are three main tricks, and you can scroll through each one below.
One machine, one drug, one weak spot.
To build the wall around each of its cells, a fungus needs a particular building-block molecule (its name is ergosterol). It makes that block using a tiny protein machine (called Cyp51). The drug slots into that machine and jams it shut. With the machine stuck, the building block never gets made, the cell wall never forms, and the fungus dies. Each trick below breaks that chain in a different place.
Three ways around the drug
There's more than one way to resist.
A resistant fungus rarely invents something new. It reuses parts it already has, in three main ways: change the shape of the machine so the drug no longer fits, pump the drug back out before it can work, or make so many copies of the machine that the drug can't jam them all.
Trick 1 · change the machine's shape
1. Change the machine's shape
Start with the drug working normally. It reaches into the machine, jams it shut, and the fungus can't make its building block.
Trick 2 · pump the drug out
2. Pump the drug out
The drug has to build up inside the cell to work. Fungal cells have pumps: parts that push unwanted molecules back outside.
Trick 3 · make more machines
3. Make more machines
A dose has only so much drug in it. Here it jams the few machines the fungus normally has.
Why it's spreading
Resistance is moving out of the clinic and onto the farm.
Candida auris
A yeast first spotted in 2009. It spreads between patients in hospitals, survives on surfaces for weeks, and often resists several antifungal drugs at once. The World Health Organization ranks it among the most urgent fungal threats.
The same drugs on crops
Close cousins of these drugs are sprayed on crops to protect them. Molds in the soil, like Aspergillus fumigatus, meet the sprays out in the field and can become resistant there, before a patient ever takes a related drug.
Almost nothing new is coming
We have only a few kinds of antifungal drug, and few new ones are close. Every trick a fungus picks up shrinks an already short list of options.
This is the gap we work on.
Telling a molecule that truly jams the machine from one that only looks like it should comes down to shape, the same shape that resistance twists to its own advantage. Measuring that shape carefully is what our drug-search work set out to prove.