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Title: β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in this paper in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding wasmore » highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. Finally, AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [3] ;  [1]
  1. Univ. of Tennessee, Knoxville, TN (United States). Dept. of Microbiology
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry and Cellular and Molecular Biology
  3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division. Center for Nanophase Materials Sciences
  4. Univ. of Maine, Orono, ME (United States). Dept. of Molecular and Biomedical Sciences
Publication Date:
Grant/Contract Number:
AC05-00OR22725; R01AL105690
Type:
Accepted Manuscript
Journal Name:
Infection and Immunity
Additional Journal Information:
Journal Volume: 85; Journal Issue: 1; Journal ID: ISSN 0019-9567
Publisher:
American Society for Microbiology
Research Org:
Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States)
Contributing Orgs:
Univ. of Maine, Orono, ME (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; β-(1,3)-glucan; adhesion force mapping; Candida albicans; Dectin-1; Young's modulus; atomic force microscopy; caspofungin; elasticity; gelatin immobilization; macrophages; indentation force mapping
OSTI Identifier:
1352801

Hasim, Sahar, Allison, David P., Retterer, Scott T., Hopke, Alex, Wheeler, Robert T., Doktycz, Mitchel J., and Reynolds, Todd B.. β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity. United States: N. p., Web. doi:10.1128/IAI.00601-16.
Hasim, Sahar, Allison, David P., Retterer, Scott T., Hopke, Alex, Wheeler, Robert T., Doktycz, Mitchel J., & Reynolds, Todd B.. β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity. United States. doi:10.1128/IAI.00601-16.
Hasim, Sahar, Allison, David P., Retterer, Scott T., Hopke, Alex, Wheeler, Robert T., Doktycz, Mitchel J., and Reynolds, Todd B.. 2016. "β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity". United States. doi:10.1128/IAI.00601-16. https://www.osti.gov/servlets/purl/1352801.
@article{osti_1352801,
title = {β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity},
author = {Hasim, Sahar and Allison, David P. and Retterer, Scott T. and Hopke, Alex and Wheeler, Robert T. and Doktycz, Mitchel J. and Reynolds, Todd B.},
abstractNote = {Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in this paper in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. Finally, AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.},
doi = {10.1128/IAI.00601-16},
journal = {Infection and Immunity},
number = 1,
volume = 85,
place = {United States},
year = {2016},
month = {11}
}