A Candida Biofilm-Induced Pathway for Matrix Glucan Delivery: Implications for Drug Resistance

PLoS Pathogens

Aaron P. Mitchell¹  Jessica Hamaker²  David R. Andes³  Hiram Sanchez³  Jeniel E. Nett³  Robert Zarnowski³  Heather T. Taff³  Kelly M. Ross³  Mike T. Cain³ 

[1] Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania;Department of Microbiology, Columbia University, New York, New York;Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin

关键词: Biofilms;    Glucans;    Extracellular matrix;    Cell walls;    Antimicrobial resistance;    C;    ida albicans;    Antifungals;    Mutant strains;   

DOI  :  10.1371/journal.ppat.1002848

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Extracellular polysaccharides are key constituents of the biofilm matrix of many microorganisms. One critical carbohydrate component of Candida albicans biofilms, β-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 β-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 distribute matrix downstream of the primary β-1,3 glucan synthase encoded by FKS1. Furthermore, our observations suggest that this matrix delivery pathway works independently from the C. albicans ZAP1 matrix formation regulatory pathway. These glucan modification enzymes appear to play a biofilm-specific role in mediating the delivery and organization of mature biofilm matrix. We propose that the discovery of inhibitors for these enzymes would provide promising anti-biofilm therapeutics.

【 授权许可】

CC BY