Some frogs secrete ‘glue’ to stop predators in their tracks

Skin-secreted adhesives, or glues, are highly effective defense mechanisms that have evolved independently in a small number of amphibians. 

From an ecological perspective, this rapidly solidifying material – essentially a sticky slime – hinders predators long enough for the prey to escape.

Glue in the animal kingdom 

But what makes some skin secretions stickier than others, and why has this trait evolved multiple times throughout amphibian history?

Adhesives, or materials that help stick things together, are ubiquitous. In everyday life, people use sticky notes or reliable rolls of tape. But what about glue in the animal kingdom? How is it used, and how does it work?

The use of biological adhesives 

In the context of glue-producing organisms, the term “biological adhesives” is used. These are naturally secreted materials found in a wide variety of species, with many playing vital roles in the organism’s survival.

The uses of these biological adhesives are as diverse as the animals producing them, including substrate attachment (as seen in sessile marine organisms like mussels, barnacles, and tubeworms), locomotion (such as the movement of starfish across the ocean floor), and prey capture (as demonstrated by spiders’ silk).

The broad taxonomic distribution of adhesive materials across several anciently diverged lineages reflects their immense utility and adaptive value.

Notably, many examples of biological adhesives come from invertebrates. But what about species more familiar to humans, such as tetrapods?

Antipredator adaptation among amphibians 

Herpetologists often recount stories about encountering frogs that excrete large amounts of slime, which rapidly becomes sticky, much like superglue. Hands stick together, the frog sticks to the hands – a very sticky situation. 

Though these stories are often anecdotal, literature on this phenomenon is relatively scarce. However, the lack of research does not make the accounts any less true.

Skin-secreted chemicals are the most widespread form of antipredator adaptation among amphibians, and in a few species, this mechanism manifests as glue. 

When stressed, the amphibian discharges a viscous fluid from its back that quickly solidifies into a sticky mass, functioning as a powerful defense tool.

Deterring predators with glue

The glue incapacitates predators, often snakes, by clogging their mouths and preventing them from swallowing the amphibian. The predator eventually abandons its attack due to the high energetic cost of overcoming the glue.

While most biochemical research has focused on toxic skin secretions, such as poisons, the study of glue remains limited. One reason for this gap may be that glue is a rare feature in frogs, evolving sporadically in species that are distantly related on the evolutionary tree.

Glue as a defense mechanism 

Frog glue has been discovered in different parts of the world, yet its absence in most species, including close relatives, is notable. 

For instance, a glue-producing frog in Madagascar may not share the island with other glue-producing amphibians from different lineages. Instead, similar sticky secretions are found in frogs distributed across regions like Australia or South America.

A recent study, published in Nature Communications, explored how glue as a defense mechanism evolved in some frogs but not others. This investigation focused on the tomato frog, Dyscophus guineti, which is endemic to Madagascar.

What makes frog glue stick?

The researchers integrated functional, molecular, and evolutionary analyses to understand what makes frog glue stick. They identified two key proteins that interact within the glue to sustain its adhesive and cohesive strength. 

One protein, PRIT (a large glycoprotein), has a glue-specific role and contains copies of an evolutionarily conserved domain found in many extracellular proteins. 

The second protein is a smaller, glycan-binding member of the galectin family, which is ubiquitous across many animals.

Structural flexibility of frog clue

The findings align with previous studies highlighting the importance of glycoproteins and glycan-binding proteins in other animal glues, though their interactions and mechanisms of action had remained unresolved until recently.

Structural models showed that while PRIT’s conserved domains are well-defined, the intervening regions are structurally heterogeneous, in contrast to most non-adhesive proteins, which are rigid and well-structured. 

This structural flexibility allows frog glue to adapt to different surfaces, such as the oral epithelia of a predator. When pressure is applied – like a predator’s bite – the fluid slime quickly transitions into a tough adhesive.

Genetic basis of frog clue

Frog glue shares a similarity with common sticky tape in that both are pressure-sensitive, requiring compressive force to activate their sticking power.

With the glue proteins identified, the study explored the genetic and structural changes that led to the evolution of glue in distantly related frog lineages. 

Interestingly, neither PRIT nor galectins are unique to D. guineti, or frogs in general. These proteins are present in all animals, including humans. 

However, the architecture of the PRIT gene evolved early in amphibian ancestors, meaning glue genes existed before the glue itself.

Parallel evolution of frog glue

Another glue-producing frog, the Mozambique rain frog (Breviceps mossambicus), also encodes a PRIT gene. Despite diverging around 100 million years ago, both Dyscophus and Breviceps descended from a poisonous ancestor, with their skin secretions evolving independently into glues.

The study also found that shifting gene expression contributed to the parallel evolution of frog glue. PRITs and galectins exhibited elevated expression levels in both glue-producing species, suggesting that regulatory changes played a crucial role in the evolution of this adhesive trait.

Unlike other glue-producing animals that evolved unique adhesion methods, these highly diverged frog lineages repeatedly recruited the same pre-existing genes by enhancing their expression.

Broader implications of the study 

The research represents the first detailed analysis of a vertebrate defense glue, expanding the understanding of these unique adaptations and paving the way for the development of new adhesive technologies.

The effectiveness of animal slimes as surgical sealants has already been demonstrated using slug defensive glue. Now, with insights into how frog glue functions, there is potential to develop new biological adhesives for medical applications, including rapid-acting surgical sealants.

Frog glue derivatives could one day become as essential in medical practices as sticky tape is in everyday households.

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