Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epithelium.
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.
Tanaka
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Division of Oral Biology and Medicine, Dental Research Institute, UCLA School of Dentistry, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA.
Miyasaki
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Lehrer
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RI
D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects*; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology; D002206:Capnocytophaga / Q000187:drug effects*; D054804:Cathelicidins; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D012965:Sodium Chloride / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D054804:Cathelicidins; D012965:Sodium Chloride