A chemical genetic screen reveals a role for proteostasis in capsule and biofilm formation by Cryptococcus neoformans.

ABSTRACT: Pathogenic microorganisms employ specialized virulence factors to cause disease. Biofilm formation and the production of a polysaccharide capsule are two important virulence factors in Cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis. Here, we show that the bipolar disorder drug lithium inhibits formation of both virulence factors by a mechanism involving dysregulation of the ubiquitin/proteasome system. By using a chemical genetics approach and bioinformatic analyses, we describe the cellular landscape affected by lithium treatment. We demonstrate that lithium affects many different pathways in C. neoformans, including the cAMP/protein kinase A, inositol biosynthesis, and ubiquitin/proteasome pathways. By analyzing mutants with defects in the ubiq

SUBMITTER: Mayer FL 

PROVIDER: S-EPMC6244295 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature