Original Article
Subject Categories: Immunology/Infection
Journal of Investigative Dermatology (2005) 125, 108–115; doi:10.1111/j.0022-202X.2005.23713.x
Anti-Fungal Activity of Cathelicidins and their Potential Role in Candida albicans Skin Infection
Belén López-García, Phillip H A Lee, Kenshi Yamasaki and Richard L Gallo
Division of Dermatology, University of California San Diego, and VA San Diego Healthcare Center, San Diego, California, USA
Correspondence: Dr Richard L. Gallo, Division of Dermatology, University of California, San Diego, and VA San Diego Healthcare System, San Diego, California 92161, USA Email: rgallo@vapop.ucsd.edu
Received 12 April 2004; Revised 28 December 2004; Accepted 1 January 2005.
Abstract
Cathelicidins have broad anti-microbial capacity and are important for host defense against skin infections by some bacterial and viral pathogens. This study investigated the activity of cathelicidins against Candida albicans. The human cathelicidin LL-37, and mouse cathelicidin mCRAMP, killed C. albicans, but this fungicidal activity was dependent on culture conditions. Evaluation of the fungal membrane by fluorescent dye penetration after incubation with cathelicidins correlated membrane permeabilization and inhibition of fungal growth. Anti-fungal assays carried out in an ionic environment that mimicked human sweat and with the processed forms of cathelicidin such as are present in sweat found that the cleavage of LL-37 to forms such as RK-31 conferred additional activity against C. albicans. C. albicans also induced an increase in the expression of cathelicidin in mouse skin, but this induction did not confer systemic or subcutaneous resistance as mCRAMP-deficient mice were not more susceptible to C. albicans in blood-killing assays or in an intradermal infection model. Therefore, cathelicidins appear active against C. albicans, but may be most effective as a superficial barrier to infection.
Keywords:
anti-microbial peptides, defensins, infection, innate immunity, LL-37, mCRAMP, sweat
Abbreviations:
CFU, colony-forming units; GAS, Group A Streptococcus; HPLC, high-pressure liquid chromatography; SG, Sytox green; SwB, sweat buffer
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