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

G3: Genes, Genomes, Genetics

Sang-Hun Oh^2¹  Won-Hee Jung^1²  Ye-Eun Son^1³ 

[1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710^3;School of Food Science and Biotechnology, Institute of Agricultural Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea^1;School of Life Science, Handong Global University, Pohang 37554, Republic of Korea^2

关键词: Cryptococcus neoformans;    calcineurin;    Crz1;    fungal virulence;    Had1;   

DOI  :  10.1534/g3.117.300444

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

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 .

【 授权许可】

CC BY