title: Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against Propionibacterium acnes.
abstract: Propionibacterium acnes is a key therapeutic target in acne, yet this bacterium has become resistant to standard antibiotic agents. We investigated whether the human antimicrobial protein granulysin is a potential candidate for the treatment of acne. Granulysin and synthetic granulysin-derived peptides possessing a helix-loop-helix motif killed P. acnes in vitro. Modification of a helix-loop-helix peptide, 31-50, by substitution of a tryptophan for the valine at amino acid 44 (peptide 31-50v44w) to increase its interaction with bacterial surfaces also increased its antimicrobial activity. Moreover, when synthesized with D- rather than L-type amino acids, this peptide (D-31-50v44w) became less susceptible to degradation by proteases and more effective in killing P. acnes. Granulysin peptides were bactericidal, demonstrating an advantage over standard bacteriostatic antibiotics in their control of P. acnes. Moreover, peptide D-31-50v44w killed P. acnes in isolated human microcomedone preparations. Importantly, peptides 31-50, 31-50v44w, and D-31-50v44w also have potential anti-inflammatory effects, as demonstrated by suppression of P. acnes-stimulated cytokine release. Taken together, these data suggest that granulysin peptides may be useful as topical therapeutic agents, providing alternatives to current acne therapies.
authors.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: McInturff
authors.forename: Shyh-Jeun
authors.initials: SJ
authors.lastname: Wang
authors.forename: Thomas
authors.initials: T
authors.lastname: Machleidt
authors.forename: T Richard
authors.initials: TR
authors.lastname: Lin
authors.forename: Ami
authors.initials: A
authors.lastname: Oren
authors.forename: Cheryl J
authors.initials: CJ
authors.lastname: Hertz
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Krutzik
authors.forename: Scott
authors.initials: S
authors.lastname: Hart
authors.forename: Karin
authors.initials: K
authors.lastname: Zeh
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Anderson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Jenny
authors.initials: J
authors.lastname: Kim
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000276:immunology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011425:Propionibacterium acnes / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C075005:GNLY protein, human; D010446:Peptide Fragments