title: 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.
abstract: 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. Proinflammatory 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.
authors.affiliation: Oral Ecology Research Group, Faculty of Dentistry, Laval University, Quebec, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Semlali
authors.forename: K P
authors.initials: KP
authors.lastname: Leung
authors.forename: S
authors.initials: S
authors.lastname: Curt
authors.forename: M
authors.initials: M
authors.lastname: Rouabhia
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology*; D015153:Blotting, Western; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D005881:Gingiva / Q000166:cytology; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism*; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering; D051193:Toll-Like Receptors / Q000378:metabolism*; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D009842:Oligopeptides; D051193:Toll-Like Receptors; D023083:beta-Defensins