Frog venom for fungal infections.

Dr. Weeks’ Comment:  As founder of the American Apitherapy Society back in 1986, I have always been intrigued with the medicinal use of venoms and poisons. As Paracelsus taught us in the 1400s:  “Poison is simply a matter of dosage” suggesting that when attenuated appropriately to a safe level, the powerful biologic forces of the poison can be medicinal. I have worked with cobra venom, spider venom, scorpion venom, warp and hornet venom but my favorite, of course, is the honey bee venom which is not only the most powerful but also the safest and readily accessible (unless we allow Monsanto to continue killing the bees with neonicotinoid pesticides). Many patients suffer with fungal infections, be they from water contamination of a home and the resulting toxic black mold or from Candida Albicans (yeast infection) related to perhaps excess sugar and antibiotic use.  I have never worked with venom from amphibians like the dart frogs, but here comes the exciting research about their venom against fungal infections.  Just remember – get the dosage right!

 

Frog skin secretions offer the first ray of hope in a deadly fungal epidemic

A few amphibians in Panama are suddenly showing signs of resistance.

frog on leaf

A Pristamantis frog in Panama

Cori Richards-Zawacki

The early 2000s were a great time to study amphibians in Panama. At night, dozens of species sang out in chorus while researchers measured and photographed frogafter frog, often hiking to remote sites hours from the nearest road. Jamie Voyles and Cori Richards-Zawacki were both graduate students at the time, just at the start of their scientific careers, and Panama’s amphibians offered a plethora of research possibilities.

There were glass frogs with transparent skin, nocturnal frogs with bulging eyes, and arboreal frogs with huge, webbed feet.

“The places where we were working had some of the most amazing amphibian diversity in the world. If you went out at night you’d see and hear dozens and dozens of different species every night, some of them amazingly beautiful,” Richards-Zawacki says.

Within a few years, everything changed. The amphibian choir grew softer, more muted, and species that had once been plentiful started vanishing.

“It wasn’t too long after the initial work in Panama when the disease appeared,” Voyles says. “We were finding dead and dying frogs in the stream. It’s hard to articulate how much of a profound experience that is. It definitely changed the trajectory of our scientific careers. On the one hand it was heartbreaking, but it was also fascinating—and that’s where we all got started.”

Over the years, the researchers continued to study the frogs and the disease that was killing them, hoping to figure out what was happening to the swiftly declining populations. Then, recently, a fraction of species at the field sites started recovering, bouncing back from the edge of annihilation. Voyles, Richards-Zawacki, and their colleagues were determined to figure out why.

dead frog

This became a common sight for researchers in Panama.

Jamie Voyles

Where is the change happening?

Chytridiomycosis is caused by the fungus Batrachochytrium dendrobatidis, which thrives in wet environments like the streams and forests of Panama.

Voyles, now a biologist at the University of Nevada, Reno, initially thought that the reason the populations were recovering was because the fungus had changed, weakening and becoming less lethal.

Richards-Zawacki, now at the University of Pittsburgh, explains that pathogens’ short life cycles often enable them to change more quickly than their hosts, reproducing in a matter of hours or days while frogs take a year to reach maturity. By cycling through generations faster, a fungus should also be able to evolve faster.

So they started their search by testing bits of the fungus, looking for variations between modern samples and those taken at the start of the outbreak. But test after test showed that the disease hadn’t changed over time. And when they introduced the pathogen to frogs in the lab, the mortality rate was a stunning 100 percent.

The pathogen hadn’t altered its deadly nature one bit.

“I was completely wrong,” Voyles says. But those experiments told them where to look next.

“That’s what made a key difference—realizing that the frogs that were still around in Panama and still infected were doing so in spite of the fact that the pathogen was still incredibly deadly. That’s really remarkable,” Voyles says. “We figured if the pathogen hasn’t changed, there must be something about the frogs that has changed.”

How they survived

The disease is a skin infection, which is especially problematic for amphibians. Their skin is the entryway for water and electrolytes, and even the gases they need to breathe. Skin care for an amphibian is a matter of life and death.

“There’s a disruption to the electrical functioning of the heart and they die from asystolic cardiac arrest,” Voyles says. It’s a kind of heart attack triggered by a chemical imbalance. The disrupted skin doesn’t allow vital components like sodium and potassium to stay in their proper proportions, so the heart stops beating.

How does a frog fight back against such fierce fungal foes? The researchers found that healthy frogs had altered their skin secretions to become more antimicrobial, and better able to fight off the fungal strain. Their study is published in this week’s Science.

golden frog

This golden frog is healthy, and survived the chytridiomycosis outbreak.

Jaime Voyles

Long road to recovery

Conservation efforts to preserve the habitat of the frogs that remain in Panama are ongoing, as researchers work to keep threatened populations from the brink of extinction.

“Recovery is possible, but it’s slow and it’s gradual,” Voyles says. “And what that means is you need to continue to monitor, to collect samples, to do the hard work that it takes to find these amphibians and see what’s going on with them.”

The skin secretions likely aren’t the only factor that has imbued some frogs with such resilience. Researchers like Voyles and Richards-Zawacki want to know more about the genetics of the host species that might have changed, and why exactly the pathogen itself hasn’t changed.

Overall, this is one of the few bright spots in what has been a harrowing epidemic for the frogs, the researchers that study them, and the people that live near them. But one bright spot doesn’t mean sunny days ahead for all frog species.

“We’re seeing pretty clear evidence that some species are showing the first signs of recovery, but it’s by no means all of the species,” Richards-Zawacki says. “Many of the frogs don’t appear to be out of the woods. Whether they will later show their own signs of recovery, we hope so. But it’s by no means back the way it was. This will continue to be a threat to species in Panama and other parts of the world.”

Richards-Zawacki and Voyles both emphasize the importance of continued, sustained monitoring to track this disease, and the effects on frog populations. Improvements in tracking epidemics like this, and changes in the interactions between pathogens and hosts, can help inform future disease tracking efforts—even for other plants and animals.

“Emerging infectious diseases are not something that’s going to go away. With increasing globalization, infectious disease will continue to be a threat, not just to wildlife but to humans as well,” Voyles says.

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Dr. Weeks’ Comment:  As founder of the American Apitherapy Society back in 1986, I have always been intrigued with the medicinal use of venoms and poisons. As Paracelsus taught us in the 1400s:  “Poison is simply a matter of dosage” suggesting that when attenuated appropriately to a safe level, the powerful biologic forces of the…
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