RL-37, an alpha-helical antimicrobial peptide of the rhesus monkey.
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.
Zhao
C
C
Department of Medicine, UCLA School of Medicine, 10833 LeConte Ave., Los Angeles, CA 90095, USA.
Nguyen
T
T
Boo
L M
LM
Hong
T
T
Espiritu
C
C
Orlov
D
D
Wang
W
W
Waring
A
A
Lehrer
R I
RI
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D054804:Cathelicidins; D002942:Circular Dichroism; D018076:DNA, Complementary / Q000032:analysis; D004926:Escherichia coli / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008253:Macaca mulatta; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013212:Staphylococcus epidermidis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D018076:DNA, Complementary; D008070:Lipopolysaccharides; D008081:Liposomes; D010446:Peptide Fragments; D011506:Proteins; C439344:RL-37 peptide; C084515:cathelin