Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum.

Andrew L Garfoot, Kacey L Dearing, Andrew D VanSchoiack, Vicki H Wysocki, Chad A Rappleye

The Journal of biological chemistry 2017 Mar 24

filter terms:

Fungal cell walls contain β-glucan polysaccharides that stimulate immune responses when recognized by host immune cells. The fungal pathogen Histoplasma capsulatum minimizes detection of β-glucan by host cells through at least two mechanisms: concealment of β-glucans beneath α-glucans and enzymatic removal of any exposed β-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 β-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-β1,3-glucanase and Eng1 is an endo-β1,3-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 post-translationally 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 β1,3-glucans; yet despite this, Exg8 does not reduce detection of yeasts by the host β-glucan receptor Dectin-1. Exg8 is largely dispensable for virulence in vivo, in contrast to Eng1. These results show that Histoplasma yeasts secrete two β1,3-glucanases and that Eng1 endoglucanase activity is the predominant factor responsible for removal of exposed cell wall β-glucans to minimize host detection of Histoplasma yeasts. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Andrew L Garfoot, Kacey L Dearing, Andrew D VanSchoiack, Vicki H Wysocki, Chad A Rappleye. Eng1 and Exg8 Are the Major β-Glucanases Secreted by the Fungal Pathogen Histoplasma capsulatum. The Journal of biological chemistry. 2017 Mar 24;292(12):4801-4810