Hasim et al. (2017) Infection and Immunity

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 cho1Delta/Delta and kre5Delta/Delta mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Delta/Delta and kre5Delta/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 kre5Delta/Delta mutant, decreased for the cho1Delta/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.

Hasim S, Allison DP, Retterer ST, Hopke A, Wheeler RT, Doktycz MJ, Reynolds TB. (2017) Beta-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity. Infection and Immunity. DOI:10.1128/IAI.00601-16