An invasive fungus that colonizes the skin of hibernating bats with fatal consequences is a stealthy invader that uses a wide range of strategies to slide into the skin cells of small mammals and silently help them survive. Uses to assist. The fungus, which causes white-nose syndrome disease, has decimated several North American species over the past 18 years.
Scientists have learned so much concerning the fungus because it was first documented in a cave in New York in 2006, including where it grows, its distribution, and its medical properties. But how the fungus initiates its infection stays a “black box — a big mystery,” says Bruce Klein, professor of pediatrics, medicine and medical microbiology and immunology on the University of Wisconsin-Madison.
This lack of know-how has made it difficult to develop preventive measures to treat or prevent infections.
Now, Klein and Marcos Isidoro-Aiza, PhD candidates in Klein's lab, have been in a position to study intimately for the primary time how the fungus penetrates and secretes cells called keratinocytes on the surface of bats' skin. Hijacks.
This feat is detailed within the July 12, 2024 issue.
The researchers found that the infected cells use it as a refuge and stop the cells from dying, which in turn suppresses the bats' immune system and allows the microbial invader to proceed growing and infecting more cells. .
To do that, Klein and Isidoro-Ayza created the primary keratinocyte cell line from the skin of a bit of brown bat. Further, they successfully simulated the conditions of hibernation, that are marked by wide fluctuations in body temperature which can be accompanied by periods of torpor — when the animal's metabolism slows and the body temperature The heat goes down — and the thrill rises.
This is crucial to understanding the infection since the cold-loving fungus takes a foothold within the cold state of torpor and is in a position to persist during arousal when the bat's body temperature rises.
Klein and Isidoro-Ayza had already identified how the fungus achieves its stealthy entry into cells: by recruiting a protein on its surface called the epidermal growth factor receptor, or EGFR. Mutations in the identical receptor in human cells cause certain lung cancers and people cancers are treated with an existing drug called gefitinib, opening up the likelihood that it may very well be used to treat white-nose syndrome. or will be done for prevention.
“Remarkably, when we blocked the receptor with this drug, we stopped the infection,” says Isidoro-Ayza. “This is an FDA-approved drug that could potentially be used to treat sensitized bats in the future.”
Although the precise role of EGFR in infection remains to be not fully understood, Klein and Isidoro-Aiza have learned so much about how the fungus works.
Its initial entry occurs during torpor, when the bat's immune system is inactive and its body temperature is in a super range for germination and growth. During torpor, the fungus penetrates the bat's skin cells with its hyphae — the skinny filaments through which it grows and collects nutrients — without breaking the cell membranes. Doing so will cause cell death and spread the fungus to the bat's immune system.
Klein and Isidoro-Ayza also found that the fungus employs a lot of strategies that allow the bats to proceed their invasion during stimulation, despite high body temperatures and reactivation of the immune system.
First, during times of stimulation, the fungus manipulates cells in order that they engulf the fungus in a process called endocytosis, fairly than the fungus using its hyphae to enter the cell. .
Second, they found that the fungus's spores — the microscopic particles by which it reproduces — are coated in a layer of melanin that protects them from the cells' strategies to kill invading microbes.
“This allows the spore to survive this period of arousal, and when the bat goes back into torpor, the spore inside its cells begins to grow again and continue to populate the skin.” says Isidoro-Ayza, a student at UW. Medicine School of Veterinary Medicine's Comparative Biomedical Sciences Graduate Program.
The ultimate infection strategy is to inhibit apoptosis, also often called programmed cell death, which is a defense mechanism that cells use to reveal pathogens in order that immune cells eradicate and destroy them. can
“By not killing the cells, the fungus can remain in the tissue and move into the deeper layers of the skin,” says Isidoro-Ayza.
With this recent knowledge, researchers are optimistic that treatments and possible vaccines are closer to becoming a reality.
The findings are only one product of a collaboration between Klein and Isidoro-Aiza and scientists on the U.S. Fish and Wildlife Service and the U.S. Geological Survey's National Wildlife Health Center in Madison. The effort received $2 million in funding from the National Science Foundation and the Paul G. Allen Family Foundation in 2023 to hunt higher insights into what causes the infection and treatment and prevention strategies against white-nose syndrome. will be prepared.
This research is worthwhile not just for the conservation of bats, which offer a lot of advantages including pollinators and bug predators, but in addition because fungal pathogens are a growing problem for a lot of species.
“There are fungal diseases that cause epidemics and epidemics in a wide variety of organisms, including plants, invertebrates, amphibians, reptiles and bats,” says Isidoro-Ayza. Therefore, any mechanisms we discover or higher understand on this disease could have implications for the conservation of other species as well.”