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LL37 and hBD-3 elevate the β-1,3-exoglucanase activity of Candida albicans Xog1p, resulting in reduced fungal adhesion to plastic.

Abstract

The opportunistic fungus Candida albicans causes oral thrush and vaginal candidiasis, as well as candidaemia in immunocompromised patients including those undergoing cancer chemotherapy, organ transplant and those with AIDS. We previously found that the AMPs (antimicrobial peptides) LL37 and hBD-3 (human β-defensin-3) inhibited C. albicans viability and its adhesion to plastic. For the present study, the mechanism by which LL37 and hBD-3 reduced C. albicans adhesion was investigated. After AMP treatment, C. albicans adhesion to plastic was reduced by up to ~60% and was dose-dependent. Our previous study indicated that LL37 might interact with the cell-wall β-1,3-exoglucanase Xog1p, which is involved in cell-wall β-glucan metabolism, and consequently the binding of LL37 or hBD-3 to Xog1p might cause the decrease in adhesion. For the present study, Xog1p(41-438)-6H, an N-terminally truncated, active, recombinant construct of Xog1p and Xog1p fragments were produced and used in pull-down assays and ELISA in vitro, which demonstrated that all constructs interacted with both AMPs. Enzymatic analyses showed that LL37 and hBD-3 enhanced the β-1,3-exoglucanase activity of Xog1p(41-438)-6H approximately 2-fold. Therefore elevated Xog1p activity might compromise cell-wall integrity and decrease C. albicans adhesion. To test this hypothesis, C. albicans was treated with 1.3 μM Xog1p(41-438)-6H and C. albicans adhesion to plastic decreased 47.7%. Taken together, the evidence suggests that Xog1p is one of the LL37/hBD-3 targets, and elevated β-1,3-exoglucanase activity reduces C. albicans adhesion to plastic.

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  • Publisher Full Text
  • Authors

    Chang HT, Tsai PW, Huang HH, Liu YS, Chien TS, Lan CY

    Institution

    Graduate Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan, Republic of China. htchang@mail.cmu.edu.tw

    Source

    The Biochemical journal 441:3 2012 Feb 1 pg 963-70

    MeSH

    Candida albicans
    Cathelicidins
    Cell Adhesion
    Cell Wall
    Cytotoxins
    Dose-Response Relationship, Drug
    Down-Regulation
    Drug Evaluation, Preclinical
    Fungal Proteins
    Glucan 1,3-beta-Glucosidase
    Humans
    Microbial Sensitivity Tests
    Organisms, Genetically Modified
    Plastics
    Protein Binding
    beta-Defensins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22023339