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Antimicrobial Agents and Chemotherapy, October 2001, p. 2695-2702, Vol. 45, No. 10
Departments of
Medicine1 and
Pediatrics2 and the Molecular
Biology Institute,3 UCLA School of Medicine,
Los Angeles, California 90095
Received 12 February 2001/Returned for modification 3 May
2001/Accepted 28 June 2001
Rhesus monkey bone marrow expresses a cathelicidin whose C-terminal
domain comprises a 37-residue alpha-helical peptide (RL-37) that
resembles human LL-37. Like its human counterpart, RL-37 rapidly
permeabilized the membranes of Escherichia coli ML-35p and
lysed liposomes that simulated bacterial membranes. When tested in
media whose NaCl concentrations approximated those of extracellular fluids, RL-37 was considerably more active than LL-37 against staphylococci. Whereas human LL-37 contains five acidic residues and
has a net charge of +6, rhesus RL-37 has only two acidic residues and a
net charge of +8. Speculating that the multiple acidic residues of
human LL-37 reduced its efficacy against staphylococci, we made a
peptide (LL-37 pentamide) in which each aspartic acid of LL-37 was
replaced by an asparagine and each glutamic acid was replaced by a
glutamine. LL-37 pentamide's antistaphylococcal activity was
substantially greater than that of LL-37. Thus, although the precursor
of LL-37 is induced in human skin keratinocytes by injury or
inflammation, its insufficiently cationic antimicrobial domain may
contribute to the success of staphylococci in colonizing and infecting
human skin.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.10.2695-2702.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
RL-37, an Alpha-Helical Antimicrobial Peptide of
the Rhesus Monkey
*
Corresponding author. Mailing address: Department of
Medicine, Room CHS 37-062, UCLA School of Medicine, 10833 LeConte Ave., Los Angeles, CA 90095-1690. Phone: (310) 825-5340. Fax: (310) 206-8766. E-mail: rlehrer{at}mednet.ucla.edu.
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