Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates

PLoS One. 2011 Mar 14;6(3):e17755. doi: 10.1371/journal.pone.0017755.

Abstract

Candida albicans is the major fungal pathogen of humans. Fungal adhesion to host cells is the first step of mucosal infiltration. Antimicrobial peptides play important roles in the initial mucosal defense against C. albicans infection. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides and is commonly expressed in various tissues and cells, including epithelial cells of both the oral cavity and urogenital tract. We found that, at sufficiently low concentrations that do not kill the fungus, LL-37 was still able to reduce C. albicans infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. Moreover, LL-37-treated C. albicans floating cells that did not adhere to the underlying substratum aggregated as a consequence of LL-37 bound to the cell surfaces. According to the results of a competition assay, the inhibitory effects of LL-37 on cell adhesion and aggregation were mediated by its preferential binding to mannan, the main component of the C. albicans cell wall, and partially by its ability to bind chitin or glucan, which underlie the mannan layer. Therefore, targeting of cell-wall carbohydrates by LL-37 provides a new strategy to prevent C. albicans infection, and LL-37 is a useful, new tool to screen for other C. albicans components involved in adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness / drug effects
  • Animals
  • Candida albicans / cytology*
  • Candida albicans / drug effects*
  • Carbohydrate Metabolism / drug effects*
  • Cathelicidins / pharmacology*
  • Cell Wall / drug effects
  • Cell Wall / metabolism*
  • Epidermal Cells
  • Epidermis / drug effects
  • Epidermis / microbiology
  • Humans
  • Mice
  • Microbial Viability / drug effects
  • Polystyrenes / pharmacology
  • Protein Binding / drug effects
  • Urinary Bladder / drug effects
  • Urinary Bladder / microbiology

Substances

  • Cathelicidins
  • Polystyrenes
  • antimicrobial peptide LL-37