title: Community participation in biofilm matrix assembly and function.
abstract: Biofilms of the fungus Candida albicans produce extracellular matrix that confers such properties as adherence and drug resistance. Our prior studies indicate that the matrix is complex, with major polysaccharide constituents being α-mannan, β-1,6 glucan, and β-1,3 glucan. Here we implement genetic, biochemical, and pharmacological approaches to unravel the contributions of these three constituents to matrix structure and function. Interference with synthesis or export of any one polysaccharide constituent altered matrix concentrations of each of the other polysaccharides. Each of these was also required for matrix function, as assessed by assays for sequestration of the antifungal drug fluconazole. These results indicate that matrix biogenesis entails coordinated delivery of the individual matrix polysaccharides. To understand whether coordination occurs at the cellular level or the community level, we asked whether matrix-defective mutant strains could be coaxed to produce functional matrix through biofilm coculture. We observed that mixed biofilms inoculated with mutants containing a disruption in each polysaccharide pathway had restored mature matrix structure, composition, and biofilm drug resistance. Our results argue that functional matrix biogenesis is coordinated extracellularly and thus reflects the cooperative actions of the biofilm community.
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and.
authors.forename: Kaitlin F
authors.initials: KF
authors.lastname: Mitchell
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Zarnowski
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and.
authors.forename: Hiram
authors.initials: H
authors.lastname: Sanchez
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Edward
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Reinicke
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and.
authors.forename: Jeniel E
authors.initials: JE
authors.lastname: Nett
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
authors.affiliation: Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706; and dra@medicine.wisc.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D018441:Biofilms; D002176:Candida albicans / Q000378:metabolism*; D002241:Carbohydrates / Q000737:chemistry; D002473:Cell Wall / Q000378:metabolism; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D015725:Fluconazole / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D008358:Mannose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D011134:Polysaccharides / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D002241:Carbohydrates; D011134:Polysaccharides; D015725:Fluconazole; D005947:Glucose; D008358:Mannose
keywords: Candida; biofilm; matrix; polysaccharide; resistance