Edited by Gerald W. HartFungal cell walls contain -glucan polysaccharides that stimulate immune responses when recognized by host immune cells. The fungal pathogen Histoplasma capsulatum minimizes detection of -glucan by host cells through at least two mechanisms: concealment of -glucans beneath ␣-glucans and enzymatic removal of any exposed -glucan polysaccharides by the secreted glucanase Eng1. Histoplasma yeasts also secrete the putative glucanase Exg8, which may serve a similar role as Eng1 in removing exposed -glucans from the yeast cell surface. Here, we characterize the enzymatic specificity of the Eng1 and Exg8 proteins and show that Exg8 is an exo-1,3-glucanase and Eng1 is an endo-1,3-glucanase. Together, Eng1 and Exg8 account for nearly all of the total secreted glucanase activity of Histoplasma yeasts. Both Eng1 and Exg8 proteins are secreted through a conventional secretion signal and are modified posttranslationally by O-linked glycosylation. Both glucanases have near maximal activity at temperature and pH conditions experienced during infection of host cells, supporting roles in Histoplasma pathogenesis. Exg8 has a higher specific activity than Eng1 for 1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host -glucan receptor Dectin-1. Exg8 is largely dispensable for virulence in vivo, in contrast to Eng1. These results show that Histoplasma yeasts secrete two 1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall -glucans to minimize host detection of Histoplasma yeasts.
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