Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans.

Published online

Journal Article

Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Cryptococcus neoformans Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets including Crz1, Pbp1, and Puf4 in C. neoformans In this study, we characterized Had1, which is one of the putative calcineurin substrates belonging to the ubiquitously conserved haloacid dehalogenase β-phosphoglucomutase protein superfamily. Growth of the had1∆ mutant was found to be compromised at 38° or higher. In addition, the had1∆ mutant exhibited increased sensitivity to cell wall perturbing agents, including Congo Red and Calcofluor White, and to an endoplasmic reticulum stress inducer dithiothreitol. Virulence studies revealed that the had1 mutation results in attenuated virulence compared to the wild-type strain in a murine inhalation infection model. Genetic epistasis analysis revealed that Had1 and the zinc finger transcription factor Crz1 play roles in parallel pathways that orchestrate stress survival and fungal virulence. Overall, our results demonstrate that Had1 is a key regulator of thermotolerance, cell wall integrity, and virulence of C. neoformans.

Full Text

Duke Authors

Cited Authors

  • Jung, W-H; Son, Y-E; Oh, S-H; Fu, C; Kim, HS; Kwak, J-H; Cardenas, ME; Heitman, J; Park, H-S

Published Date

  • February 2, 2018

Published In

Volume / Issue

  • 8 / 2

Start / End Page

  • 643 - 652

PubMed ID

  • 29233914

Pubmed Central ID

  • 29233914

Electronic International Standard Serial Number (EISSN)

  • 2160-1836

Digital Object Identifier (DOI)

  • 10.1534/g3.117.300444

Language

  • eng

Conference Location

  • United States