Characterization of Aspergillus nidulans α-glucan synthesis: roles for two synthases and two amylases

Cell walls are essential for fungal survival and growth. Fungal walls are similar to 90% carbohydrate, mostly types not found in humans, making them promising targets for anti-fungal drug development. Echinocandins, which inhibit the essential beta-glucan synthase, are already clinically available. In contrast, alpha-glucan, another abundant fungal cell wall component has attracted relatively little research attention because it is not essential for most fungi. Aspergillus nidulans has two a-glucan synthases (AgsA and AgsB) and two alpha-amylases (AmyD and AmyG), all of which affect alpha-glucan synthesis. Gene deletion showed that AgsB was the major synthase. In addition, AmyG promoted alpha-glucan synthesis whereas AmyD had a repressive effect. The lack of alpha-glucan had no phenotypic impact on solid medium, but reduced conidial adhesion during germination in shaken liquid. Moreover, alpha-glucan level correlated with resistance to Calcofluor White. Intriguingly, overexpression of agsA could compensate for the loss of agsB at the alpha-glucan level, but not for phenotypic defects. Thus, products of AgsA and AgsB have different roles in the cell wall, consistent with agsA being mainly expressed at conidiation. These results suggest that alpha-glucan contributes to drug sensitivity and conidia adhesion in A. nidulans, and is differentially regulated by two synthases and two amylases.