Candida glabrata Transcription Factor Rpn4 Mediates Fluconazole Resistance through Regulation of Ergosterol Biosynthesis and Plasma Membrane Permeability

Author:

Pais Pedro12,Califórnia Raquel12,Galocha Mónica12,Viana Romeu12,Ola Mihaela3,Cavalheiro Mafalda12,Takahashi-Nakaguchi Azusa4,Chibana Hiroji4,Butler Geraldine3ORCID,Teixeira Miguel C.12ORCID

Affiliation:

1. Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal

2. iBB-Institute for Bioengineering and Biosciences, Biological Sciences Research Group, Instituto Superior Técnico, Lisbon, Portugal

3. School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, Dublin, Ireland

4. Medical Mycology Research Center, Chiba University, Chiba, Japan

Abstract

The ability to acquire azole resistance is an emblematic trait of the fungal pathogen Candida glabrata . Understanding the molecular basis of azole resistance in this pathogen is crucial for designing more suitable therapeutic strategies. This study shows that the C. glabrata transcription factor (TF) CgRpn4 is a determinant of azole drug resistance. RNA sequencing during fluconazole exposure revealed that CgRpn4 regulates the expression of 212 genes, activating 80 genes and repressing, likely in an indirect fashion, 132 genes.

Funder

Programa Operacional Regional de Lisboa 2020

MEC | Fundação para a Ciência e a Tecnologia

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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