Novel Entries in a Fungal Biofilm Matrix Encyclopedia

Author:

Zarnowski Robert1,Westler William M.2,Lacmbouh Ghislain Ade3,Marita Jane M.4,Bothe Jameson R.3,Bernhardt Jörg56,Lounes-Hadj Sahraoui Anissa7,Fontaine Joël7,Sanchez Hiram1,Hatfield Ronald D.4,Ntambi James M.38,Nett Jeniel E.19,Mitchell Aaron P.10,Andes David R.19

Affiliation:

1. Department of Medicine, Infectious Diseases, University of Wisconsin, Madison, Wisconsin, USA

2. National Magnetic Resonance Facility at Madison, University of Wisconsin, Madison, Wisconsin, USA

3. Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, USA

4. Dairy Forage Research Center, U.S. Department of Agriculture, Madison, Wisconsin, USA

5. Universitat Institute for Microbiology, Ernst Moritz Arndt University, Greifswald, Germany

6. DECODON GmbH, BioTechnikum Greifswald, Germany

7. Université du Littoral Côte d’Opale, Unité de Chimie Environnementale at Interactions sur le Vivant, Calais, France

8. Department of Food Sciences, University of Wisconsin, Madison, Wisconsin, USA

9. Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA

10. Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA

Abstract

ABSTRACT Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. We further explore the function of matrix components, including the impact on drug resistance. We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. Three individual polysaccharides were identified and were suggested to interact physically. Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). Functional matrix proteomic analysis revealed 458 distinct activities. The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. IMPORTANCE This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle.

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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