Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils.
Turner. J J; Cho. Y Y; Dinh. N N NN; Waring. A J AJ; Lehrer. R I RI
Key Findings
- LL-37 inhibits many bacteria (E. coli, P. aeruginosa, S. aureus, etc.) at <10 µg/ml, though high salt reduces activity against some strains
- It disrupts both outer and inner membranes of E. coli and binds LPS with high affinity (cooperative binding)
- In the presence of bacterial lipids, LL-37 changes from a random coil to an alpha‑helix, enhancing its antimicrobial action
Practical Outcomes
- The findings highlight LL-37’s strong antimicrobial potential, but there’s no ready‑to‑use supplement or dosage for self‑experimentation. For biohackers, the take‑away is that boosting the body’s own LL-37 (e.g., via vitamin D or other known inducers) might support skin and airway defenses, though any direct application would need further safety and formulation work.
Summary
LL-37 is a natural protein from white blood cells that can kill a wide range of bacteria, including some antibiotic‑resistant strains, at fairly low doses. Its ability to break bacterial membranes and bind toxic bacterial components (LPS) suggests it helps protect skin and possibly lungs, especially in conditions like cystic fibrosis, but the study only tests it in lab dishes, not in people.
Abstract
Human neutrophils contain two structurally distinct types of antimicrobial peptides, beta-sheet defensins (HNP-1 to HNP-4) and the alpha-helical peptide LL-37. We used radial diffusion assays and an improved National Committee for Clinical Laboratory Standards-type broth microdilution assay to compare the antimicrobial properties of LL-37, HNP-1, and protegrin (PG-1). Although generally less potent than PG-1, LL-37 showed considerable activity (MIC, <10 microgram/ml) against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus, and vancomycin-resistant enterococci, even in media that contained 100 mM NaCl. Certain organisms (methicillin-resistant S. aureus, Proteus mirabilis, and Candida albicans) were resistant to LL-37 in media that contained 100 mM NaCl but were susceptible in low-salt media. Burkholderia cepacia was resistant to LL-37, PG-1, and HNP-1 in low- or high-salt media. LL-37 caused outer and inner membrane permeabilization of E. coli ML-35p. Chromogenic Limulus assays revealed that LL-37 bound to E. coli O111:B4 lipopolysaccharide (LPS) with a high affinity and that this binding showed positive cooperativity (Hill coefficient = 2.02). Circular dichroism spectrometry disclosed that LL-37 underwent conformational change in the presence of lipid A, transitioning from a random coil to an alpha-helical structure. The broad-spectrum antimicrobial properties of LL-37, its presence in neutrophils, and its inducibility in keratinocytes all suggest that this peptide and its precursor (hCAP-18) may protect skin and other tissues from bacterial intrusions and LPS-induced toxicity. The potent activity of LL-37 against P. aeruginosa, including mucoid and antibiotic-resistant strains, suggests that it or related molecules might have utility as topical bronchopulmonary microbicides in cystic fibrosis.
Study Information
pubmed
1998
10.1128/aac.42.9.2206