1. ^*Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
2. ^†Ansata Therapeutics, Inc., La Jolla, California, USA
3. ^‡Division of Pulmonary & Critical Care Medicine, Department of Medicine, West Los Angeles Veterans Administration Medical Center, Los Angeles, California, USA
4. ^§Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
5. ^¶Department of Microbiology, Immunology, Molecular Genetics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA
6. ^#Howard Hughes Medical Institute, Los Angeles, California, USA
7. ^**UCLA-DOE Institute of Genomics and Proteomics, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, USA
8. ^††Division of Dermatology, University of California San Diego, San Diego, California, USA
9. ^‡‡Veterans Administration San Diego Healthcare System, San Diego, California, USA

Correspondence: Jenny Kim MD, PhD, Division of Dermatology, University of California Los Angeles 52-121 CHS 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. Email: JeKim@mednet.ucla.edu

¹Explora BioLabs, La Jolla, California, USA.

Received 28 October 2004; Revised 18 March 2005; Accepted 21 March 2005.

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.