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The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogen Candida albicans

Misty R. Peterson, Robert Jordan Price, Sarah Gourlay, Alisha May, Jennifer Tullet, View ORCID ProfileAlessia Buscaino
doi: https://doi.org/10.1101/340364
Misty R. Peterson
aKent Fungal Group, School of Biosciences, University of Kent, Canterbury, United Kingdom
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Robert Jordan Price
aKent Fungal Group, School of Biosciences, University of Kent, Canterbury, United Kingdom
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Sarah Gourlay
aKent Fungal Group, School of Biosciences, University of Kent, Canterbury, United Kingdom
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Alisha May
aKent Fungal Group, School of Biosciences, University of Kent, Canterbury, United Kingdom
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Jennifer Tullet
aKent Fungal Group, School of Biosciences, University of Kent, Canterbury, United Kingdom
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Alessia Buscaino
aKent Fungal Group, School of Biosciences, University of Kent, Canterbury, United Kingdom
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  • ORCID record for Alessia Buscaino
  • For correspondence: A.Buscaino@kent.ac.uk
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ABSTRACT

The human fungal pathogen Candida albicans is responsible for millions of infections annually. Due to the few available anti-fungal drugs and the increasing incidence of drug resistance, the number of C. albicans infections is dramatically increasing. Morphological switches, such as the white-opaque switch and the yeast-hyphae switch, are key for the development of C. albicans pathogenic traits. Lysine deacetylases are emerging as important regulators of morphological switches. Yet, targeting lysine deacetylases for drug development is problematic due to the high homology between the fungal and human proteins that could result in toxicity. Here we provide evidence that the fungal specific proteins Hda2 and Hda3 interact with the lysine deacetylase Hda1. By combining phenotypic analyses with genome-wide transcriptome analyses, we demonstrate that Hda2 and Hda3 control C. albicans morphological switches. Under nutrient-rich conditions, deletion of HDA2 or HDA3 leads to moderate overexpression of the master regulator of white-opaque switching WOR1 and increase switching frequency. Under hyphae inducing conditions, deletion of HDA2 and HDA3 block hyphae development. However, deletion of HDA2 and HDA3 does not affect hyphae-formation and virulence in vivo. We propose that Hda2 and Hda3 are good targets for the development of anti-fungal drugs to be used in combination therapy.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 07, 2018.
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The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogen Candida albicans
Misty R. Peterson, Robert Jordan Price, Sarah Gourlay, Alisha May, Jennifer Tullet, Alessia Buscaino
bioRxiv 340364; doi: https://doi.org/10.1101/340364
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The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogen Candida albicans
Misty R. Peterson, Robert Jordan Price, Sarah Gourlay, Alisha May, Jennifer Tullet, Alessia Buscaino
bioRxiv 340364; doi: https://doi.org/10.1101/340364

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