期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：13
页码：4092-4097
DOI：10.1073/pnas.1421437112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCandida albicans is the most common fungal pathogen and frequently grows as a biofilm. These adherent communities tolerate extremely high concentrations of antifungals due in large part to the protective extracellular matrix. The present studies observe a novel reliance on multiple matrix constituents for structure and function. Furthermore, the results demonstrate how the biofilm community assembles these matrix components in the extracellular space. Our findings reveal a coordinated mechanism by which the defining trait of the biofilm lifestyle arises and identify a number of potential therapeutic targets. 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 -mannan, {beta}-1,6 glucan, and {beta}-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.
