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The ER protein translocation channel subunit Sbh1 controls virulence of Cryptococcus neoformans

ABSTRACT: C. neoformans is an opportunistic human pathogen whose polysaccharide capsule anchored to the cell wall is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with protein translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins, Sec61, Sbh1, and Sss1. Sbh1 is most divergent and contains multiple phosphorylation sites which may allow it to control entry into the secretory pathway in a regulated, species- and protein-specific manner. We show here that in contrast to S. cerevisiae, C. neoformans lacking SBH1 are barely temperature-sensitive, but that absence of SBH1 causes a cell-wall defect in both species. Comparison of the proteomes of wildtype and Δsbh1 C. neoformans revealed a small set of secretory and transmembrane proteins whose expression under infection-like conditions was upregulated in wildtype, but not in the Δsbh1 mutant. These proteins are mostly involved in cell-wall biogenesis. We found that adhesion to macrophages was compromised in the Δsbh1 strain and in mice, the C. neoformans Δsbh1 mutant was virtually avirulent. We conclude that upon contact with the host Sbh1 controls entry of virulencefactors into the secretory pathway of Cryptococcus neoformans.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Cryptococcus Neoformans Var. Grubii Serotype A (strain H99 / Atcc 208821 / Cbs 10515 / Fgsc 9487) (filobasidiella Neoformans Var. Grubii)

TISSUE(S): Cell Culture

SUBMITTER: Jennifer Geddes-McAlister

LAB HEAD: Jennifer Geddes-McAlister

PROVIDER: PXD013894 | Pride | 2023-01-27

REPOSITORIES: Pride

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