Why common midwife toads survive deadly fungus in the Pyrenees

Around four mountain lakes in the Pyrenees, the same small toad has encountered the same lethal fungus. Yet the outcomes have been strikingly different.

At one lake, the toads have almost disappeared. At the other three, they continue to thrive alongside the pathogen that nearly wiped out their neighbours.

The toad, the fungus and the mountain range are the same in each case.

Why do some populations collapse while others recover? A team led by University College London (UCL) has offered a new answer.

The research drew on field and laboratory expertise from the Zoological Society of London (ZSL). Researchers at Imperial College London helped link the patterns of disease to the toads’ immune chemistry.

How common midwife toads respond to the fungus

The species is the common midwife toad, a mountain-dwelling amphibian found in parts of western Europe. The fungus is Batrachochytrium dendrobatidis, known as Bd.

Across the world, Bd has caused catastrophic declines in frogs and toads. It attacks their skin, disrupting their ability to regulate water, salts and minerals, and infected animals often die.

In the Western Pyrenees, every studied population of these toads crashed after Bd arrived. Around 19 years later, two different patterns had emerged.

At three lakes, the toads had come to coexist with Bd and their numbers remained stable. At the fourth, Lac d’Arlet, repeated waves of deaths continued to push them towards local extinction.

Why metamorphosis brings danger

The fungus has an unusual limitation: it cannot take hold in a tadpole.

Bd feeds on keratin, the tough protein found in adult amphibian skin. Tadpoles lack keratinised skin, leaving the fungus with nowhere to live.

Metamorphosis changes that. As a tadpole becomes a toad and its skin hardens, Bd can establish itself and the disease can become deadly.

This is also the stage at which the immune system is supposed to mature. The collision of these two major changes makes it the most dangerous period in a young toad’s life.

More peptides than expected

The team examined antimicrobial peptides: short chains of amino acids in the slimy coating on a toad’s skin, which serve as a first line of defence.

To examine the full mixture, the researchers used mass spectrometry, a technique that measures the weight of molecules with great precision.

The mixture proved far richer than expected. Of the 1,152 peptides found in the skin secretions, only seven had previously been described.

“The ability to analyse hundreds to thousands of molecules in parallel has only emerged over the past decade,” said Dr Kersti Karu of UCL Chemistry.

“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.”

Peptides doing surprising work

A large arsenal is not necessarily an effective one. When the researchers tested the toad’s known peptides against Bd in the laboratory, most had no effect on the fungus.

Just a handful, belonging to a family known as the alyteserins, slowed Bd. Their effectiveness differed, with a couple standing out as clearly the most potent.

The way they worked was unexpected, too. Peptides of this kind usually kill by making holes in an invader’s outer membrane, but these instead slipped inside the fungal cells.

Timing matters more than life stage

The crucial distinction between a protected toad and a vulnerable one was not whether it was a tadpole or an adult.

Some tadpoles already had a rich, protective mixture of peptides, while some young adults still had a limited set without the alyteserins that fight Bd.

The struggling Lac d’Arlet population contained many of these underprepared young adults. They had reached the keratin-skinned stage before their defences had caught up.

“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,” said Dr Phillip Jervis, who led the study.

“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.”

Why some tadpoles mature early

The team cannot yet say with certainty what determines that timing, although it has a strong lead.

Midwife toad tadpoles are unusual: in cold mountain lakes, some remain larvae for a winter or longer before changing.

That slower path may give a tadpole more time to build its defences before it develops vulnerable adult skin.

“The next step is to look at what factors prevent these immune systems from maturing early,” said Dr Phillip Jervis.

“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.”

Broader implications of the study

“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,” said Professor Alethea Tabor of UCL Chemistry.

“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.”

The wider finding offers hope: even a species badly affected by Bd can possess the tools to survive. For these toads, the difference between collapse and recovery may lie in a few weeks of a young animal’s development.