Dermcidin-derived peptides show a different mode of action than the cathelicidin LL-37 against Staphylococcus aureus.
Dermcidin (DCD) is an antimicrobial peptide which is constitutively expressed in eccrine sweat glands. By postsecretory proteolytic processing in sweat, the DCD protein gives rise to anionic and cationic DCD peptides with a broad spectrum of antimicrobial activity. Many antimicrobial peptides induce membrane permeabilization as part of their killing mechanism, which is accompanied by a loss of the bacterial membrane potential. In this study we show that there is a time-dependent bactericidal activity of anionic and cationic DCD-derived peptides which is followed by bacterial membrane depolarization. However, DCD-derived peptides do not induce pore formation in the membranes of gram-negative and gram-positive bacteria. This is in contrast to the mode of action of the cathelicidin LL-37. Interestingly, LL-37 as well as DCD-derived peptides inhibit bacterial macromolecular synthesis, especially RNA and protein synthesis, without binding to microbial DNA or RNA. Binding studies with components of the cell envelope of gram-positive and gram-negative bacteria and with model membranes indicated that DCD-derived peptides bind to the bacterial envelope but show only a weak binding to lipopolysaccharide (LPS) from gram-negative bacteria or to peptidoglycan, lipoteichoic acid, and wall teichoic acid, isolated from Staphylococcus aureus. In contrast, LL-37 binds strongly in a dose-dependent fashion to these components. Altogether, these data indicate that the mode of action of DCD-derived peptides is different from that of the cathelicidin LL-37 and that components of the bacterial cell envelope play a role in the antimicrobial activity of DCD.
Department of Dermatology, University of Tübingen, Liebermeisterstr. 25, D-72076 Tübingen, Germany.
Ilknur
I
Senyürek
Maren
M
Paulmann
Tobias
T
Sinnberg
Hubert
H
Kalbacher
Martin
M
Deeg
Thomas
T
Gutsmann
Marina
M
Hermes
Thomas
T
Kohler
Fritz
F
Götz
Christiane
C
Wolz
Andreas
A
Peschel
Birgit
B
Schittek
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004269:DNA, Bacterial / Q000378:metabolism; D054805:Dermcidins / Q000378:metabolism / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D004269:DNA, Bacterial; D054805:Dermcidins; D012329:RNA, Bacterial; D054804:Cathelicidins