Antimicrobial peptides of innate immunity

Reading time: ~2 min · Part of the free certification in peptide science

Long before antibodies, organisms defended themselves with antimicrobial peptides (AMPs): short, cationic, amphipathic molecules present in skin, mucosa and immune cells.

How they kill microbes

• Electrostatic attraction: their positive charge draws them to bacterial membranes, rich in negative phospholipids. Human membranes, with more cholesterol and a neutral outer face, are much less vulnerable.
• Membrane disruption: they insert and form pores or destabilize the bilayer («barrel-stave», «toroidal pore» and «carpet» models).
• Intracellular targets: some inhibit protein or nucleic acid synthesis.

Because they attack the membrane rather than a specific enzyme, resistance emerges more slowly than with many conventional antibiotics, which makes them interesting as a line of research.

Main families in humans

• α and β defensins: rich in cysteines and disulfide bridges; present in neutrophils, the intestine and the skin.
• Cathelicidin LL-37: the only human cathelicidin. Besides its antimicrobial action, it modulates the immune response (chemotaxis, activation of dendritic cells), interferes with biofilm formation and takes part in wound healing.

Limits

Their activity in the laboratory does not translate easily to systemic use: they are rapidly degraded by proteases, can be toxic at high concentrations and their immunomodulatory effect is double-edged (excess LL-37 has been associated with inflammatory skin diseases such as rosacea and psoriasis).

Educational content for scientific purposes. It distinguishes preclinical from clinical evidence and is not medical advice, diagnosis or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).