Cathelicidin Antimicrobial Peptide
LL-37

The Discovery

The Invisible Army

A Question Nobody Was Asking

Every year, millions of people around the world die from infections that antibiotics can no longer treat. But long before this crisis began, a Swedish scientist named Hans Boman asked a question that most people ignored: How do insects survive without immune systems like ours?

Insects have no antibodies. No white blood cells that remember past infections. Yet flies, moths, and beetles thrive in some of the filthiest environments on Earth. Boman suspected they had a secret weapon.

In 1972, he injected bacteria into the pupae of giant silk moths called Hyalophora cecropia. Instead of dying, the moths produced something remarkable — tiny proteins that killed bacteria on contact. By 1981, Boman's team had isolated the first-ever animal antimicrobial peptide. They named it cecropin, after the moth that made it.

The scientific world barely noticed. Antibiotics were everywhere. Why would anyone care about bug juice?

The Breakthrough

The Human Discovery

We Had the Weapon All Along

Inspired by Boman's work, his former student Birgitta Agerberth at the Karolinska Institutet began hunting for similar peptides in humans. In 1995, her team made a stunning discovery: a gene in human bone marrow coded for a peptide they called FALL-39 — named after its first four amino acids.

Just one year later, Gudmundur Gudmundsson showed that the active form of the peptide was actually two amino acids shorter than they first thought. He renamed it LL-37 — 'LL' for the two leucine amino acids at its front, and '37' for its total length.

What made LL-37 special was that it was the only member of the cathelicidin family found in humans. Other mammals have dozens. Humans have just this one — and it turned out to be incredibly versatile. It could kill bacteria, call immune cells to an infection site, and even help heal damaged tissue.

LL-37 wasn't just an antibiotic. It was a conductor directing the entire immune orchestra.

The Trials

The Swiss Army Knife

More Than Just a Killer

Through the early 2000s, researchers around the world kept discovering new things that LL-37 could do. Richard Gallo at UC San Diego showed it was critical for skin defense — people whose bodies made too little LL-37 were more likely to develop eczema and chronic skin infections.

Other labs found that LL-37 didn't just kill bacteria — it punched holes in their cell walls like a molecular drill. Because bacterial walls are negatively charged and LL-37 is positively charged, the peptide is attracted to bacteria like a magnet. Human cells have a different structure, so LL-37 leaves them mostly unharmed.

Perhaps most exciting was the vitamin D connection. Scientists discovered that vitamin D tells your body to make more LL-37. This finally explained why people with low vitamin D get sick more often — their natural antibiotic production was turned down.

LL-37 was also found in sweat, saliva, breast milk, and the lining of your lungs and gut. It was everywhere — a first responder stationed at every entrance to your body.

The Crisis

The Superbug Crisis

When Modern Medicine Starts Failing

By the 2010s, the antibiotic crisis had become impossible to ignore. MRSA — a staph infection that resists most antibiotics — was killing tens of thousands of people every year in hospitals. Drug companies had largely stopped developing new antibiotics because they weren't profitable enough.

The World Health Organization warned that the world was heading toward a 'post-antibiotic era' where simple infections could become deadly again. Researchers desperately needed a new approach.

This was when LL-37 went from a curiosity to a potential lifesaver. Unlike traditional antibiotics, bacteria struggle to develop resistance to LL-37. The reason? LL-37 attacks the basic structure of bacterial walls — something bacteria can't easily change without destroying themselves. After millions of years of exposure to cathelicidins, bacteria still haven't figured out how to fully resist them.

But LL-37 had its own problems. It was expensive to make, broke down quickly in the body, and could cause side effects at high doses. The dream of using it as a drug was still years away from reality.

The Legacy

The New Frontier

From Lab Bench to Bedside

Clinical trials have now tested LL-37 in humans for hard-to-heal wounds like venous leg ulcers — chronic sores that affect millions of elderly people. A randomized trial showed the peptide was safe and showed promising results, especially for larger wounds that traditional treatments couldn't fix.

Researchers are also engineering shorter, more stable versions of LL-37 that keep its bacteria-killing power but last longer in the body. Some teams are packaging it in tiny nanoparticles to deliver it exactly where it's needed.

The tuberculosis connection has opened another exciting door. Since vitamin D boosts LL-37 production, clinical trials are testing whether vitamin D supplements combined with drugs that boost LL-37 can help fight TB — especially in countries where the disease remains a leading killer.

After decades in the shadows of conventional antibiotics, humanity's own natural defense peptide is finally getting its chance to shine. In a world running out of antibiotics, LL-37 represents something rare: a weapon that evolution has been sharpening for 500 million years.