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The Frogs That Never Got Infected: Michael Zasloff and the Discovery of Magainins
In the 1980s, a researcher named Michael Zasloff noticed a puzzle in a tank of African clawed frogs. The frogs had been through surgery. They were living in water that was far from sterile. By every expectation, their wounds should have become infected. They healed instead.
Key takeaways
- Zasloff, then at the US National Institutes of Health, was working with Xenopus frogs whose eggs are widely used in research.
- He realized the frogs’ skin must contain a defense against microbes and set out to find it.
- In 1987 his group reported magainins, peptides of about 23 amino acids with a helical shape.
- Magainins work by damaging bacterial membranes, a very different mechanism from most antibiotics.
- A lab-designed relative, pexiganan, was tested for infected diabetic foot ulcers but was not approved.
A clue in the tank
African clawed frogs have been laboratory animals for decades. Their large eggs make them excellent for studying cells. Zasloff, who was working with them, observed that frogs which had been operated on to remove eggs recovered without trouble, even though the water in the tanks was not kept sterile.
A less curious observer might have shrugged. Zasloff reasoned that the skin or the wound must produce something that stops bacteria growing, and he decided to look for it.
Finding the peptides
By extracting frog skin and testing fractions against bacteria, his group isolated two related peptides. They named them magainins, from a Hebrew word for shield. The peptides were about 23 amino acids long. In water they are loose, but when they touch a bacterial membrane they curl into a helix with one side that likes fat and one side that likes water.
That shape is the key. Bacterial membranes have a negative charge on the surface, and magainins carry a positive charge, so they stick. Once in contact, they disturb the membrane and the bacterium leaks and dies.
A different kind of antibiotic
Most antibiotics block a specific protein inside the bacterium. Antimicrobial peptides often act on the membrane instead, which is harder for bacteria to change quickly. That is why they attracted so much interest as the world began to worry about resistance. The idea that animals, plants and insects all carry peptides like this changed how people think about innate immunity.
The long road to the clinic
A company was formed to develop a synthetic version, and a modified magainin called pexiganan was tested as a topical treatment for infected foot ulcers in people with diabetes. In the late 1990s the results were reviewed by US regulators. The peptide worked, but it performed about as well as an oral antibiotic rather than clearly better, and it was not approved.
Peptide antibiotics have had a hard path for practical reasons: they can be broken down by enzymes, they may be expensive to make, and their action on membranes can affect host cells too. Those problems are the same ones discussed in half-life engineering.
What the lab can take from it
Magainins are still used as models for understanding how peptides interact with membranes. They are a good example of why small changes in charge and shape produce big changes in behavior, a theme in our isoelectric point post and our post on aggregation.
They also show why careful research on wound models matters. Our guide to a wound healing experiment checklist and skin research models explains how researchers design these studies.
The bottom line
Zasloff’s discovery began with a simple question about a tank of healthy frogs. Good research often starts that way. Explore the research compounds in our catalog and read the lab reports before you decide what fits your protocol.
Related reading
- Wound healing experiment checklist
- Skin research models
- Half-life engineering
- Browse the full Research Library
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For laboratory research use only. Not for human or veterinary use, and not intended to diagnose, treat, cure or prevent any condition. This article is educational and is not medical advice.