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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2018-02-01
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| Series: | G3: Genes, Genomes, Genetics |
| Subjects: | |
| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.117.300444 |
| _version_ | 1818889955962781696 |
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| author | Won-Hee Jung Ye-Eun Son Sang-Hun Oh Ci Fu Hye Shin Kim Jin-Hwan Kwak Maria E. Cardenas Joseph Heitman Hee-Soo Park |
| author_facet | Won-Hee Jung Ye-Eun Son Sang-Hun Oh Ci Fu Hye Shin Kim Jin-Hwan Kwak Maria E. Cardenas Joseph Heitman Hee-Soo Park |
| author_sort | Won-Hee Jung |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T17:17:15Z |
| format | Article |
| id | doaj.art-13d6b9169abd42b3b12d5ec78a1f4f17 |
| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-19T17:17:15Z |
| publishDate | 2018-02-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-13d6b9169abd42b3b12d5ec78a1f4f172022-12-21T20:12:49ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362018-02-018264365210.1534/g3.117.30044423Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformansWon-Hee JungYe-Eun SonSang-Hun OhCi FuHye Shin KimJin-Hwan KwakMaria E. CardenasJoseph HeitmanHee-Soo ParkCalcineurin 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.http://g3journal.org/lookup/doi/10.1534/g3.117.300444Cryptococcus neoformanscalcineurinCrz1fungal virulenceHad1 |
| spellingShingle | Won-Hee Jung Ye-Eun Son Sang-Hun Oh Ci Fu Hye Shin Kim Jin-Hwan Kwak Maria E. Cardenas Joseph Heitman Hee-Soo Park Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans G3: Genes, Genomes, Genetics Cryptococcus neoformans calcineurin Crz1 fungal virulence Had1 |
| 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 | Cryptococcus neoformans calcineurin Crz1 fungal virulence Had1 |
| url | http://g3journal.org/lookup/doi/10.1534/g3.117.300444 |
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