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Antimicrobial Agents and Chemotherapy, June 2009, p. 2499-2509, Vol. 53, No. 6
0066-4804/09/$08.00+0 doi:10.1128/AAC.01679-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Dermcidin-Derived Peptides Show a Different Mode of Action than the Cathelicidin LL-37 against Staphylococcus aureus
Ilknur Senyürek,1
Maren Paulmann,1
Tobias Sinnberg,1
Hubert Kalbacher,2
Martin Deeg,3
Thomas Gutsmann,4
Marina Hermes,5
Thomas Kohler,7
Fritz Götz,6
Christiane Wolz,7
Andreas Peschel,7 and
Birgit Schittek1*
Department of Dermatology, University of Tübingen, Tübingen, Germany,1 Medical and Natural Sciences Research Center, University of Tübingen, Tübingen, Germany,2 Section for Transplantation Immunology and Immunohematology, University of Tübingen, Tübingen, Germany,3 Research Center Borstel, Leibniz Center for Medicine and Biosciences, Division of Biophysics, Borstel, Germany,4 Department of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany,5 Microbial Genetics, University of Tübingen, Tübingen, Germany,6 Medical Microbiology and Hygiene Institute, University of Tübingen, Tübingen, Germany7
Received 19 December 2008/ Returned for modification 13 March 2009/ Accepted 1 April 2009
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.
* Corresponding author. Mailing address: Department of Dermatology, Eberhard-Karls-University Tübingen, Liebermeisterstr. 25, D-72076 Tübingen, Germany. Phone: 49-7071-2980832. Fax: 49-7071-295187. E-mail: birgit.schittek{at}med.uni-tuebingen.de
Published ahead of print on 3 April 2009.
Antimicrobial Agents and Chemotherapy, June 2009, p. 2499-2509, Vol. 53, No. 6
0066-4804/09/$08.00+0 doi:10.1128/AAC.01679-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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