a candida biofilm-induced pathway for matrix glucan delivery implications for drug resistance一个假丝酵母biofilm-induced通路矩阵葡聚糖交付对耐药性的影响.pdfVIP

A Candida Biofilm-Induced Pathway for Matrix Glucan Delivery: Implications for Drug Resistance 1 1 1 1 1 1 Heather T. Taff , Jeniel E. Nett , Robert Zarnowski , Kelly M. Ross , Hiram Sanchez , Mike T. Cain , 2 3 1 Jessica Hamaker , Aaron P. Mitchell , David R. Andes * 1 Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, 2 Department of Microbiology, Columbia University, New York, New York, 3 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania Abstract Extracellular polysaccharides are key constituents of the biofilm matrix of many microorganisms. One critical carbohydrate component of Candida albicans biofilms, b-1,3 glucan, has been linked to biofilm protection from antifungal agents. In this study, we identify three glucan modification enzymes that function to deliver glucan from the cell to the extracellular matrix. These enzymes include two predicted glucan transferases and an exo-glucanase, encoded by BGL2, PHR1, and XOG1, respectively. We show that the enzymes are crucial for both delivery of b-1,3 glucan to the biofilm matrix and for accumulation of mature matrix biomass. The enzymes do not appear to impact cell wall glucan content of biofilm cells, nor are they necessary for filamentation or biofilm formation. We demonstrate that mutants lacking these genes exhibit enhanced susceptibility to the commonly used antifungal, fluconazole, during biofilm growth only. Transcriptional analysis and biofilm phenotypes of strains with multiple mutations suggest that these enzymes act in a complementary fashion to