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

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. neoform...

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Autores principales: Jung, Won-Hee, Son, Ye-Eun, Oh, Sang-Hun, Fu, Ci, Kim, Hye Shin, Kwak, Jin-Hwan, Cardenas, Maria E., Heitman, Joseph, Park, Hee-Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919746/
https://www.ncbi.nlm.nih.gov/pubmed/29233914
http://dx.doi.org/10.1534/g3.117.300444
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author Jung, Won-Hee
Son, Ye-Eun
Oh, Sang-Hun
Fu, Ci
Kim, Hye Shin
Kwak, Jin-Hwan
Cardenas, Maria E.
Heitman, Joseph
Park, Hee-Soo
author_facet Jung, Won-Hee
Son, Ye-Eun
Oh, Sang-Hun
Fu, Ci
Kim, Hye Shin
Kwak, Jin-Hwan
Cardenas, Maria E.
Heitman, Joseph
Park, Hee-Soo
author_sort Jung, Won-Hee
collection PubMed
description 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.
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spelling pubmed-59197462018-04-27 Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans Jung, Won-Hee Son, Ye-Eun Oh, Sang-Hun Fu, Ci Kim, Hye Shin Kwak, Jin-Hwan Cardenas, Maria E. Heitman, Joseph Park, Hee-Soo G3 (Bethesda) Investigations 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. Genetics Society of America 2017-12-12 /pmc/articles/PMC5919746/ /pubmed/29233914 http://dx.doi.org/10.1534/g3.117.300444 Text en Copyright © 2018 Jung et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Jung, Won-Hee
Son, Ye-Eun
Oh, Sang-Hun
Fu, Ci
Kim, Hye Shin
Kwak, Jin-Hwan
Cardenas, Maria E.
Heitman, Joseph
Park, Hee-Soo
Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
title Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
title_full Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
title_fullStr Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
title_full_unstemmed Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
title_short Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
title_sort had1 is required for cell wall integrity and fungal virulence in cryptococcus neoformans
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919746/
https://www.ncbi.nlm.nih.gov/pubmed/29233914
http://dx.doi.org/10.1534/g3.117.300444
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