title: Disruption of sphingolipid biosynthetic gene IPT1 reduces Candida albicans adhesion and prevents activation of human gingival epithelial cell innate immune defense.
abstract: We demonstrated the effect of a Candida albicans sphingolipid biosynthetic gene, IPT1, on the interaction between gingival epithelial and Candida cells using monolayer cultures and engineered human oral mucosa tissue (EHOM). Disrupting the IPT1 gene greatly reduced Candida adhesion to gingival epithelial cells, compared to the wild-type and revertant strains. The yeasts adhesion to epithelial cells may activate toll-like receptors (TLRs). Cell response against Candida infection was thus investigated by evaluating TLR expression and antimicrobial peptide (AMP) production. The wild-type and revertant strains both activated TLR2, TLR4, TLR6, and TLR9 gene expression in the epithelial cells, whereas the Δipt1 mutant Candida strain had no effect on this expression. This finding was supported by an increased AMP expression (human β-defensin HBD-2 and HBD-3) in the EHOM tissue infected with the wild-type and revertant Candida strains, and a decreased expression in the Δipt1 mutant-infected model. HBD protein secretion confirmed the absence of any effect by the Δipt1 on epithelial cell innate defense. This is the first study to demonstrate that a disruption of the IPT1 gene affects Candida-host interaction, thus preventing TLR activation and β-defensin expression.
authors.affiliation: Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec City, Québec, Canada. mahmoud.rouabhia@fmd.ulaval.ca
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Rouabhia
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.forename: Ali Abdul
authors.initials: AA
authors.lastname: Lattif
authors.forename: Sèverine
authors.initials: S
authors.lastname: Curt
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Chandra
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism*; D002176:Candida albicans / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006801:Humans; D009061:Mouth Mucosa / Q000382:microbiology; D016254:Mutagenesis, Insertional; D009924:Organ Culture Techniques; D013107:Sphingolipids / Q000096:biosynthesis; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D005656:Fungal Proteins; C503746:IPT1 protein, Candida albicans; D013107:Sphingolipids; D051193:Toll-Like Receptors; D037521:Virulence Factors