title: Resistance to dermcidin-derived peptides is independent of bacterial protease activity.
abstract: Dermcidin (DCD) is an antimicrobial peptide constitutively expressed in eccrine sweat glands in human skin. By post-secretory proteolytic processing in sweat, the DCD protein gives rise to anionic and cationic DCD peptides that are able to kill several Gram-positive and Gram-negative bacteria but are only weakly active against Pseudomonas aeruginosa. Here, we questioned whether bacterial resistance to DCD peptides is mediated by proteolytic degradation. It was shown that DCD-derived peptides are degraded by purified bacterial proteases and by extracellular proteases secreted by P. aeruginosa in a concentration-dependent manner. However, protease-deficient mutants of P. aeruginosa PAO1 lacking either lasA, lasB (elastase) or both showed a similar sensitivity towards DCD-derived peptides as the wild-type strain. Finally, inhibition of total protease activity indicated that proteases secreted by P. aeruginosa are not responsible for the poor activity of DCD-derived peptides against P. aeruginosa. These data suggest that the decreased sensitivity of P. aeruginosa to DCD-derived peptides is not mediated by proteolytic degradation under physiological conditions.
authors.affiliation: Department of Dermatology, University of Tübingen, Tübingen, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Senyürek
authors.forename: G
authors.initials: G
authors.lastname: Döring
authors.forename: H
authors.initials: H
authors.lastname: Kalbacher
authors.forename: M
authors.initials: M
authors.lastname: Deeg
authors.forename: A
authors.initials: A
authors.lastname: Peschel
authors.forename: C
authors.initials: C
authors.lastname: Wolz
authors.forename: B
authors.initials: B
authors.lastname: Schittek
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010447:Peptide Hydrolases / Q000235:genetics; D010455:Peptides / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010455:Peptides; C442243:dermcidin; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa