How a fungus causes deadly disease in North American bats

Researchers might have a solution to white-nose syndrome, a disease which has killed millions of North American bats since it was first reported in 2007.

The science behind the findings is fascinating.

White-nose syndrome is caused by the fungus Pseudogymnoascus destructans, which infects the skin cells (keratinocytes) of hibernating bats. It affects multiple species, but the once ubiquitous and now endangered little brown bat (Myotis lucifugus) is one of the most susceptible.

Little is known about how the fungus initiates infection, making it challenging to develop countermeasures to treat or prevent infection.

For the first time, researchers from the University of Wisconsin–Madison in the US have studied exactly how P. destructans gains entry and covertly hijacks keratinocytes at the surface of bats’ skin.

They have identified an existing drug, gefitinib, that reduces this invasion in cell cultures and could potentially be used to treat or prevent the disease.

P. destructans is a psychrophilic, or cold-loving, fungus that grows best at temperatures between 12-16°C.

During hibernation, bats undergo multiple cycles of body temperature fluctuations between torpor (cold phase) and arousal (warm phase). White-nose syndrome causes bats to rouse more frequently, which consumes their limited fat stores and causes them to die from starvation.

The researchers cultured bat keratinocytes at different temperatures to mimic these conditions in the lab.

They found that the fungus uses a protein, epidermal growth factor receptor (EGFR), on the surface of keratinocytes to enter the cell.  Mutations in the same receptor in human cells drive certain lung cancers, which are treated with gefitinib.

“Remarkably, when we inhibited the receptor with this drug, we stopped the infection,” says PhD candidate Marcos Isidoro-Ayza, first author of the study in Science.

“This is an FDA-approved drug that could potentially be used in the future for the treatment of susceptible bat species.”

They also found the fungus initially enters during torpor, when bats’ immune systems are dormant and their body temperature is in an ideal range for P. destructans to germinate and grow. 

During torpor, the fungus penetrates bats’ skin cells with its hyphae — slender filaments through which it grows and gathers nutrients — without breaking the cells’ membranes. 

To avoid detection during periods of arousal, the fungus then manipulates the cells so they engulf it in a process known as endocytosis. The spores are also coated in a layer of melanin that protects them from the cells’ strategies for killing invading microbes.

“That allows the spore to survive that period of arousal, and when the bat goes back into torpor, the spores inside of its cells start germinating again and keep colonising the skin,” says Isidoro-Ayza.

P. destructans also blocks programmed cell death (apoptosis) in keratinocytes, preventing clearance of infected cells.

“By not killing the cells, the fungus can linger in the tissue and go into deeper layers of the skin,” says Isidoro-Ayza.

With their new findings, the researchers are hopeful that treatments and a potential vaccine are closer to becoming reality.