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Antimicrobial Agents and Chemotherapy, October 2001, p. 2695-2702, Vol. 45, No. 10
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

Chengquan Zhao,1 Tung Nguyen,1 Lee Ming Boo,1 Teresa Hong,1 Cesar Espiritu,1 Dmitri Orlov,1 Wei Wang,1 Alan Waring,1,2 and Robert I. Lehrer1,3,*

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.


* 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.


Antimicrobial Agents and Chemotherapy, October 2001, p. 2695-2702, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2695-2702.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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