4.4 Article

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

期刊

INFECTION AND IMMUNITY
卷 85, 期 1, 页码 -

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00601-16

关键词

beta-(1,3)-glucan; adhesion force mapping; Candida albicans; Dectin-1; Young's modulus; atomic force microscopy; caspofungin; elasticity; gelatin immobilization; macrophages; indentation force mapping

资金

  1. U.S. DOE Office of Biological and Environmental Research Genomic Science Program under the Plant-Microbe Interfaces Scientific Focus Area at Oak Ridge National Laboratory
  2. U.S. Department of Energy [DEAC0500OR22725]
  3. University of Tennessee-Oak Ridge National Laboratory (UT-ORNL) Joint Institute for Biological Sciences
  4. NIAID [NIH-1 R01AL105690]

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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 beta-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for beta-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of beta-(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 live cells with atomic force microscopy (AFM). Two mutants, the cho1 Delta/Delta and kre5 Delta/Delta mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1 Delta/Delta and kre5 Delta/Delta 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 kre5 Delta/Delta mutant, decreased for the cho1 Delta/Delta 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. 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.

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