The long-term objective of this proposal is to develop effective antimicrobial peptides as a new therapeutic modality for the treatment of acne. The increase in antibiotic-resistant strains of Propionibacterium acnes, the bacterium that contributes to the pathogenesis of acne, has hastened research for development of novel therapeutic agents. We hypothesize that the body's own natural antimicrobial peptides may be useful therapeutic agents in the treatment of acne. Our preliminary data indicate that the human-derived antimicrobial protein granulysin appears in acne lesions during the resolution phase, is effective at killing P. acnes and blocks P. acnes-induced monocyte cytokine release. We propose experiments to study the antimicrobial and antiinflammatory activity of granulysin-derived peptides, and predict their efficacy as toprincipal investigatorcal agents in the treatment of acne.
Our specific aims are to 1) identify and engineer antimicrobial peptides that are effective at killing P. acnes, 2) identify peptides that have anti-inflammatory properties since peptides that have both antimicrobial activity and anti-inflammatory properties would be ideal therapeutic candidates, and, 3) determine the ability of granulysin-derived peptides to penetrate skin and microcomedones. These studies will have the potential to develop a new class of antibiotic compounds for use in the treatment of cutaneous infections ncluding acne vulgaris as well as other skin infections in which bacteria are involved. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI059091-03
Application #
7212205
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Korpela, Jukka K
Project Start
2005-07-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$366,235
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Friedman, Adam J; Phan, Jenny; Schairer, David O et al. (2013) Antimicrobial and anti-inflammatory activity of chitosan-alginate nanoparticles: a targeted therapy for cutaneous pathogens. J Invest Dermatol 133:1231-9
Cho, John S; Zussman, Jamie; Donegan, Niles P et al. (2011) Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections. J Invest Dermatol 131:907-15
Liu, Philip T; Phan, Jenny; Tang, Dominic et al. (2008) CD209(+) macrophages mediate host defense against Propionibacterium acnes. J Immunol 180:4919-23