Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epithelium.
Tanaka. D D; Miyasaki. K T KT; Lehrer. R I RI
Key Findings
- LL-37 kills Actinobacillus actinomycetemcomitans and Capnocytophaga spp. at 7.5‑11.6 µg/ml (≈99% kill).
- High salt (≈400 mM NaCl) completely stops LL‑37’s killing ability; normal physiological salt already reduces it.
- Serum (10‑15% human AB serum) blocks LL‑37 activity, while pentamide‑37 is less affected.
Practical Outcomes
- Because saliva and blood contain salt and proteins that inhibit LL‑37, using the native peptide as an oral rinse or supplement is unlikely to be effective now. Modified forms like pentamide‑37 may overcome this inhibition, so future products could target oral infections, but more development is needed.
Summary
LL-37, a natural antimicrobial peptide, can kill certain oral bacteria at low concentrations, but its effect disappears when there’s a lot of salt or blood‑type proteins around. A slightly altered version, pentamide‑37, works a bit better in those conditions, hinting it could be a more useful drug in the future.
Abstract
The bactericidal activity of synthetic LL-37, a cathelicidin, was assessed against Actinobacillus actinomycetemcomitans (three strains) and Capnocytophaga spp. (three strains). All strains were sensitive to LL-37, and exhibited 99% effective dose of 7.5-to-11.6 micrograms/ml. An amidated form of LL-37, pentamide-37, killed with about the same efficacy as LL-37. Partial inhibition of killing was noted at physiologic concentrations of NaCl, and complete inhibition was observed at 400 mM NaCl. At approximately the 99% effective dose--i.e., 10 micrograms/ml--LL-37 also lost activity against A. actinomycetemcomitans in the presence of native or heat-inactivated 10-15% normal human AB serum. Pentamide-37 was less sensitive to serum inhibition than LL-37. In conclusion, certain oral, gram-negative bacteria are sensitive to the bactericidal activity of LL-37 at low concentrations of serum and salt, a condition likely to be found within the membrane-delimited phagolysosome. Modified forms of LL-37, such as pentamide-37, may be more suitable for future therapeutic application in the presence of serum.
Study Information
pubmed
2000
10.1034/j.1399-302x.2000.150403.x