Scientists have uncovered why some amphibian populations rebound after being devastated by a deadly fungal disease that has wiped out frogs and toads around the world.
The research, led by University College London (UCL), ZSL, and Imperial College London, found that the timing of an amphibian’s immune development plays a critical role in whether it survives infection. The findings were published in the journal Nature Chemical Biology.
A Deadly Fungus That Targets Adult Amphibians
The chytrid fungus, Batrachochytrium dendrobatidis (Bd), has caused catastrophic declines in amphibian populations across the globe. The fungus is responsible for chytridiomycosis, a disease that damages the skin of frogs and toads and disrupts their ability to regulate water, salts, and minerals.
Young amphibians are largely protected because tadpoles and larvae lack the keratin rich skin that Bd feeds on. Once they transform into adults and their skin becomes keratinized, they become vulnerable to infection, often leading to mass die offs.
To better understand why some populations recover while others continue to collapse, researchers studied common midwife toads living around four lakes in the Pyrenees of France and Spain that had all experienced severe Bd outbreaks.
At one lake, the toad population was still declining and had nearly disappeared. At the other three lakes, however, the populations had rebounded even though the fungus remained present in the environment.
Early Immune Defenses Make the Difference
The team focused on antimicrobial peptides, which are natural chemicals released from amphibian skin that serve as an important part of their immune system.
They discovered that toads from the recovering populations developed these protective peptides much earlier, while they were still tadpoles. By the time they reached adulthood and became susceptible to Bd, their immune defenses were already well established.
In contrast, toads from the struggling population produced far fewer of these protective peptides during the tadpole stage, leaving them less prepared once they matured.
Lead author Dr. Phillip Jervis, of UCL Chemistry, ZSL Institute of Zoology and Imperial College London, said: “Our study shows species that have declined heavily from this disease can still recover. They have the tools to fight off infection — it just depends on timing. The disease kills toads and frogs as they turn from tadpoles to adults. Getting mature immunity at the tadpole stage helps these toads survive and the population to continue.”
Dr. Jervis added: “The next step is to look at what factors prevent these immune systems from maturing early. This could be down to genetics or environmental factors such as temperature or the presence of trout — a major danger for tadpoles that could drive them to develop into adults faster so they can leave the water, meaning less time for their immune system to develop.”
More Than 1,100 Hidden Immune Peptides Discovered
To investigate the toads’ chemical defenses, the researchers used mass spectrometry to examine the mixture of peptides (short chains of amino acids) released from their skin.
The analysis revealed a much larger collection of immune peptides than scientists had anticipated. Of the 1,152 peptides identified, only seven had previously been documented.
The study also found that tadpoles producing a wider variety of peptides (i.e., their defenses had matured prior to becoming toads) were much more likely to survive despite ongoing Bd outbreaks. Populations with fewer peptides during the tadpole stage continued to suffer high death rates.
Findings Could Inspire Future Medicines
Senior author Professor Alethea Tabor (UCL Chemistry) said: “We discovered a far greater diversity of peptides than we expected. We now need to understand how they work to control pathogens and which ones are anti-microbial.
“A lot of medicines for humans were initially found in the natural world — penicillin came from fungi, for example. So these peptides are new leads that could be used to help human health, especially as we have our own problems as a species with the rise of antimicrobial resistance, which is requiring us to find new ways to treat infections.”
Mass spectrometry allows scientists to measure the mass of molecules with exceptional precision. In this study, researchers used tandem mass spectrometry at UCL Chemistry to break peptides into smaller fragments, measure those fragments, and reconstruct each peptide’s structure. This process enabled the team to identify and sequence hundreds of previously unknown molecules.
Co-author Dr. Kersti Karu (UCL Chemistry) said: “The ability to analyze hundreds to thousands of molecules in parallel has only emerged over the past decade. This approach is more commonly applied in human health research, for example to distinguish cancer cells from normal tissue, but is increasingly being extended to other areas of biological investigation.”
The research was funded by the UK’s Natural Environment Research Council (NERC) and the Leverhulme Trust.