Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2011-05, Vol.32 (5), p.859-867
• Main Authors: Semlali, A., Leung, K.P., Curt, S., Rouabhia, M.
• Format: Article
• Language: English
• Subjects: Adhesion; amphotericin B; Anti-Infective Agents - adverse effects; Anti-Infective Agents - pharmacology; Antimicrobial peptide; Attenuation; beta-Defensins - metabolism; Biological and medical sciences; Blotting, Western; Candida; Candida albicans; Candida albicans - drug effects; Candida albicans - pathogenicity; cell adhesion; Cell Adhesion - drug effects; cell culture; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Cytokines; Cytokines - metabolism; epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Fundamental and applied biological sciences. Psychology; Gingiva - cytology; Human; Humans; Innate immunity; interleukin-1beta; interleukin-6; KSL-W; Mouth Mucosa - drug effects; Mouth Mucosa - metabolism; mucosa; Oligopeptides - adverse effects; Oligopeptides - pharmacology; Peptides; Receptors; Reverse Transcriptase Polymerase Chain Reaction; secretion; Tissue Engineering; TLRs; Toll-like receptors; Toll-Like Receptors - metabolism; toxicity; Vertebrates: endocrinology; Virulence; yeasts; β-Defensins
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2011.01.020

► Synthetic antimicrobial decapeptide KSL-W had no toxic effect on cell adhesion or growth. ► Pre-treating Candida albicans with KSL-W attenuated the yeast's virulence as demonstrated by a reduction of Candida adhesion to and growth on engineered human oral mucosa. ► KSL-W pre-treated Candida was unable to activate Toll-like receptor and human β-defensin mRNA expression. ► KSL-W controls Candida virulence through pro-inflammatory cytokines (IL-1β and IL-6) but in different manners. ► KSL-W effects were comparable to amphotericin B. We investigated the toxicity of synthetic antimicrobial decapeptide KSL-W on normal human gingival epithelial cell cultures, its effect on Candida albicans adhesion and growth, and the activation of epithelial cell innate immunity. Our results indicate that KSL-W had no toxic effect on cell adhesion or growth, suggesting its safe use with human cells. Pre-treating C. albicans with KSL-W attenuated the yeast's virulence as demonstrated by its reduced adhesion and growth on engineered human oral mucosa epithelium and the subsequent decreased expression of some innate defense molecules by targeted epithelial cells. Indeed, the expression of Toll-like receptors and human β-defensins was reduced in tissues infected with KSL-W-treated Candida. Proinflammtory cytokine secretion (IL-1β and IL-6) by the epithelial cells was also regulated by KSL-W in a manner similar to that of antifungal molecule amphotericin B. These findings therefore show that KSL-W is safe for use with human cells and is able to attenuate Candida virulence by modulating its effects on host innate immunity. This study proposes the potential application of KSL-W peptide as an alternative antifungal agent.