WITHA guy in camping gear, headlights piercing the shadows, Carolina Muñoz and her teammates trudged through the dense foliage of Colombia's Amazon jungle in search of slippery fluorescent treasures, while trying to dodge the thorns of chonta palms and rattan vines, as well as the fangs of venomous snakes. When they finally spotted their prey, she and her team froze to avoid spooking it. They then plucked the lime green and blue frog—the Orinoco lime tree frog—from a tree branch and placed it in a fabric bag, where it remained, wrapped in foliage and water mist, until it was ready to go to its new home.
It was just one of many amphibians that the team of frog hunters collected over a five-year period, repeating the process in forests, mountains and wetlands, even in urban areas across the country. In total, they collected two frogs from 50 different species. Every frog they caught carried the promise of a cure hidden in its skin.
Back at the lab at the University of the Andes in Bogota, Muñoz and his colleagues swabbed the frogs' bodies and collected the sticky mucus they secreted to test for chemicals that could cure human diseases.
They had good reason to believe that they would succeed. Frog skin is be surprised nature. The mucous membrane, this outer layer remains moist and is filled with a mixture of chemicals that frogs have developed over millennia of evolution. It is thin, delicate and highly permeable, allowing frogs to use it to inhale oxygen when they are submerged and to spit out toxins that kill infections and poison predators when they are attacked.
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During her fieldwork in the Amazon, in addition to plump green Orinoco linden tree frogs, Muñoz collected, among others, Boulenger's warty backpack frogs and tiger-striped whistling frogs known as ra assobiadora. When she took them to her lab, she discovered that the skin of all three frog species was filled with new-to-science peptides—small protein fragments—that could help cells fight the virus. yellow fever virusa viral disease spread by mosquitoes throughout much of Africa and South America that causes severe flu-like symptoms. In cells treated with the peptide, infectious activity decreased by 35 percent.
It turns out that Orinoco lime frogs secrete peptides known as phrenatin And Buforin IIwhich can clog bacterial membranes and DNA. And her skin tests on 11 other frogs and toads from her field work. disclosed some molecules that can destroy human leukemia cancer cells.
Frog secretions may even promote wound healing.
Muñoz initially thought she could find the most powerful antidotes for human diseases in frogs living in the deepest reaches of the jungle. But she soon realized that those who lived closer to human settlements (like a specimen of the Orinoco linden tree frog she picked up from a playground in an Amazonian city) were more likely to be exposed to the same pathogens as humans and therefore produce toxins that could be beneficial to us. “The frogs we captured near human activity contained peptides that were 10 times or more more potent than those far away from humans,” Muñoz says. However, she still has a lot of work to do: “We have identified about 70 peptides, but have only published reports on two or three,” she says.
Muñoz is not the only one who has looked for antiviral, anticancer and antibacterial agents in frog skin. Researchers at Emory University in Atlanta also discovered that mucus produced by the skin of some frogs may act as an antidote. influenza virusand maybe even for COVID-19.
Elsewhere, scientists are studying jaguar frogs and Kuatun frogs discovered peptides that act as both antimicrobial and anticancer molecules. For example, the skin of a jaguar frog is washed in water. peptide which in a Petri dish eats away human lung cancer, breast cancer, prostate cancer and brain cancer cells. It also produces the same effects, albeit less pronounced, in real mice without many of the toxic side effects.
Some researchers have found that frog secretions may even promote wound healing. Team in China analyzed skin secretions The Yunnan stinking frog, a stinking frog found in South Asia, was discovered in a petri dish to contain a peptide that can stimulate the proliferation of human skin cells and speed up wound healing in the skin of real mice. The skin secretions of the East Asian bullfrog, known in Chinese traditional medicine, were also examined. shown contain a peptide that can heal wounds, like mucus from leather Asian black-backed toad. Ideally, these organic molecules could be used to create creams, gels and other topical treatments that help heal burns or chronic wounds, such as those that some people with diabetes develop.
Frog skin is “an extremely fertile source for drug development,” says Michael Zasloff, the first scientist to describe antimicrobial peptides in frog skin in the late 1980s. He studied Evolution of frog skin peptides all over the world.
But it's one thing to make a molecule fight bacteria or cancer in cell culture, and quite another to make it work in the human body. Almost all of the above studies were carried out in the laboratory in petri dishes: this is the very first step in drug development. “When the peptide gets into the bloodstream, it now explores membranes all over the place,” Zasloff says. “It has to be selective enough to ignore all those membranes” and focus on its target: a disease-causing molecule floating in the blood of a living organism.
The few tests performed on mice are also difficult to extrapolate to humans, Zazloff adds. “You have to go from mouse to man. That's the problem, isn't it?”
However, the excitement surrounding these discoveries is not just about what the peptides do, but also how they do it.
Frog skin is “an extremely fertile source for drug development.”
Many of the peptides found in frog skin are positively charged, whereas bacterial cell membranes are composed of negatively charged lipids. As a result, these peptides, under the influence of an electrostatic charge, are attracted to bacterial membranes and, when colliding with the membrane, destroy it. (Don't worry, these peptides aren't as attracted to cell membranes instead in animals and plants, which are mostly neutrally charged.) peptides buforin II and phrenatin For example, found in the skin of the Orinoco tree frog, they kill bacteria by penetrating the membranes of bacterial cells and altering their genetics by binding to DNA and RNA. This is true for many of the peptides found in the jaguar frog, the Chinese frog, and many others.
“It’s wonderful and exciting for me,” says Muñoz, who also wrote paper about these types of peptides in Nature in 2024.
With antibiotic resistance on the rise, scientists are racing to find new therapeutic compounds, and the ones hiding on the frog's back may have a unique advantage. Antibiotics typically target bacterial enzymes, and enzymes can mutate and adapt over time, reducing their vulnerability, but bacteria themselves do not have the same shape-shifting abilities, so they cannot adapt to membrane-disrupting antidotes. Likewise, these peptides act through multiple mechanisms simultaneously; They not only destroy the bacterial membrane, but also enter the cell and bind to its genetic material, making it much more difficult for bacteria to develop resistance.
“Unlike traditional antibiotics, which act on a single pathway, these peptides act on multiple fronts,” Muñoz says.
Most importantly, although antimicrobial peptides are much more gentle on human cell membranes than on bacterial membranes (since human cell membranes are neutrally charged), they can still penetrate these membranes, entering the cell without destroying it. It is this selective interaction that makes them so promising as tools for delivering genes or drugs inside a human cell. According to Muñoz, peptides act as keys that unlock the cell membrane and direct the therapeutic payload to its destination, as if the peptide is starting the engine of a truck full of drugs, allowing the delivery system to enter the cell and direct the treatment exactly where it needs to go.
“These molecules can help ensure that the cargo is delivered to the correct position in the nucleus,” Muñoz says.
This special power gives frog skin molecules a whole new biotechnological use, Muñoz says, and it's where she's focused most of her efforts lately. Having recently left behind a time when she collected frogs from tree branches in the jungle, Muñoz is now working on using artificial intelligence to help predict which of these molecules might have the best chance of fighting disease in huge quantities, and studying and developing ways in which they can enter human cells in smart and effective ways.
Despite the difficulties in getting these compounds from the laboratory to the pharmacy, it appears that the world of frog peptides still has something to share. In a sense, Muñoz has swapped the jungle canopy for a digital one—using AI to predict which frog-created molecules might one day jump from petri dishes to patients.
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Main image: Reptiles4all / Shutterstock.
