Toad Brains Fight Deadly Microbes

Biological Strategy

Large-webbed bell toad

Mary Hoff

Protect From Microbes

In living systems, microbes play important roles, such as breaking down organic matter and maintaining personal and system health. But they also pose threats. Bacteria can be pathogens that cause diseases. Some bacteria create colonies called biofilms that can coat surfaces, reducing their effectiveness–for example, inhibiting a leaf’s ability to photosynthesize. Living systems must have strategies for protecting from microbes that cause disease or become so numerous that they create an imbalance in the system. At the same time, living systems must continue living in harmony with other microbes. Some living systems kill microbes. Others repel without killing to reduce the chances that microbes will adapt to the lethal strategy and become resistant to it. For example, some pea seedlings exude a chemical that inhibits biofilm buildup.

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Protect From Fungi

Fungi–which include molds and mushrooms, amongst others–play important roles in every ecosystem, but can also create diseases in plants and animals. Fungi can rapidly reproduce, so living systems must fend them off early to avoid their spread and potential, physical harm. Living systems use both physical and chemical strategies to protect from fungi, and must ensure that these strategies don’t harm the threatened living system itself. For example, a pumpkin’s skin has antifungal proteins to prevent fungal growth without harming the pumpkin itself.

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Amphibians

Class Amphibia (“to live a double life”): Frogs, salamanders, toads

Amphibians live a “double life” by being able to survive both on land and in water. Unlike reptiles with dry, scaly skin, amphibians have smooth skin that needs to be kept moist. Many live in the water through development and start life with gills, and then transition to breathing with lungs. They can get even more oxygen through cutaneous respiration, or breathing through their skin. This class represents the first animal group to be able to efficiently walk on land—aided by the well-defined limbs that gave them a “leg up” on their finned competitors.

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Antimicrobial peptides protect the brains of fire-bellied toads from microbes.

Introduction

Fire-bellied toads (Bombina species), found in Asia and Europe, get their name from their brightly-colored undersides. Two of the species, the large-webbed bell toad (B. maxima) and the small-webbed bell toad (B. microdeladigitora) share another noteworthy trait in addition to their name and coloration: Their brains contain large numbers of antimicrobial peptides (AMPs), a class of powerful germ-killing molecules.

The Strategy

AMPs are not in themselves rare or unusual molecules. Made of various combinations of short-chain amino acids, the building blocks of proteins, they are found in most living things. These amino acids have different segments that can penetrate the different layers of a cell membrane. This gives them the ability to poke holes in the membranes surrounding bacteria and microscopic fungi in a variety of different ways, causing the cells’ contents to leak out and the microbes to die. AMPs usually target the cell membrane itself, rather than interacting with receptors on the membrane surface. As a result, it is much more difficult for microbes to evolve resistance to AMPs compared with conventional antibiotics.

Amphibians in particular are known for their abundant AMPs. Lacking hair or scales, these animals rely directly on their skin surface to protect them from germs. And AMPs help the skin deliver: In many species, external glands secrete AMPs onto the skin, where they can attach to and destroy infection-causing microorganisms. Scientists have identified some 300 or more kinds of AMPs on frogs alone. But it turns out that could be just the tip of the iceberg. When scientists decided to look for AMPs elsewhere, they found signs of 52 kinds of AMPs in the large-webbed bell toad’s brain and 27 in the brain of its small-webbed relative. Of these, 59 are AMPs that have never been seen elsewhere. Some were only effective against a very limited set of microorganisms. Others were able to knock off multiple kinds of bacteria as well as fungi.

Scientists suspect that the AMPs found in the toads’ brains are helping protect them from infections that could harm their nervous systems. They also think that the difference in the kinds of AMPs found in the brains of the two species tested may be related to the different types of microbes found in the toads’ respective habitats, with B. maxima more likely to encounter germs found in ponds and B. microdeladigitora needing defense against those found in trees.

The Potential

The newly discovered AMPs in these toads’ brains open the door to a better understanding of how these small molecules can so effectively kill microbes. Because they can exist in the brain without harming brain tissue, they also offer an opportunity for gaining insights into how to make effective antimicrobial therapies that destroy germs without harming our own bodies. And they offer insights into how humans might develop new strategies for overcoming bacteria that have developed resistance to conventional antibiotics, with particular attention to those that attack human brains, causing life-threatening infections such as meningitis and encephalitis.