title: Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance.
abstract: Biofilms are a protected niche for microorganisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm models formed on bioprosthetic materials, we demonstrated that biofilm formation proceeds through three distinct developmental phases. These growth phases transform adherent blastospores to well-defined cellular communities encased in a polysaccharide matrix. Fluorescence and confocal scanning laser microscopy revealed that C. albicans biofilms have a highly heterogeneous architecture composed of cellular and noncellular elements. In both models, antifungal resistance of biofilm-grown cells increased in conjunction with biofilm formation. The expression of agglutinin-like (ALS) genes, which encode a family of proteins implicated in adhesion to host surfaces, was differentially regulated between planktonic and biofilm-grown cells. The ability of C. albicans to form biofilms contrasts sharply with that of Saccharomyces cerevisiae, which adhered to bioprosthetic surfaces but failed to form a mature biofilm. The studies described here form the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance and provide the means to design novel therapies for biofilm-based infections.
authors.affiliation: Center for Medical Mycology, University Hospitals of Cleveland, and Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chandra
authors.forename: D M
authors.initials: DM
authors.lastname: Kuhn
authors.forename: P K
authors.initials: PK
authors.lastname: Mukherjee
authors.forename: L L
authors.initials: LL
authors.lastname: Hoyer
authors.forename: T
authors.initials: T
authors.lastname: McCormick
authors.forename: M A
authors.initials: MA
authors.lastname: Ghannoum
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D019904:Polymethyl Methacrylate; D012828:Silicones
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D012828:Silicones; D019904:Polymethyl Methacrylate