ß-glucan unmasking in some Candida albicans mutants correlates with increases in cell wall surface roughness and decreases in cell wall elasticity
Sahar Hasim, David P. Allison, Scott T. Retterer, Alex Hopke, Robert T. Wheeler, Mitchel J. Doktycz, and Todd B. Reynolds
29 December 2016, Infection and Immunity 85(1): e00601-16; doi: 10.1128/IAI.00601-16
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 ß- (1, 3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for ß- (1, 3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of ß- (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, cho1Δ/Δ and kre5Δ/Δ, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of cho1Δ/Δ and kre5Δ/Δ to 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 binding force of Dectin-1 to all of the strains was similar, but the frequency of binding was highest for kre5Δ/Δ, decreased for cho1Δ/Δ and rare for wild type. These data show that nanoscale changes in surface topology correlate 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.
Sahar Hasim, David P. Allison, Scott T. Retterer, Alex Hopke, Robert T. Wheeler, Mitchel J. Doktycz, and Todd B. Reynolds. (2016). ß-glucan unmasking in some Candida albicans mutants correlates with increases in cell wall surface roughness and decreases in cell wall elasticity. Infect. Immun. IAI.00601-16; doi:10.1128/IAI.00601-16