Identification and functional characterization of Rca1, a transcription factor involved in both antifungal susceptibility and host response in Candida albicans.

Eukaryotic Cell
Patrick VandeputteDominique Sanglard

Abstract

The identification of novel transcription factors associated with antifungal response may allow the discovery of fungus-specific targets for new therapeutic strategies. A collection of 241 Candida albicans transcriptional regulator mutants was screened for altered susceptibility to fluconazole, caspofungin, amphotericin B, and 5-fluorocytosine. Thirteen of these mutants not yet identified in terms of their role in antifungal response were further investigated, and the function of one of them, a mutant of orf19.6102 (RCA1), was characterized by transcriptome analysis. Strand-specific RNA sequencing and phenotypic tests assigned Rca1 as the regulator of hyphal formation through the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway and the transcription factor Efg1, but also probably through its interaction with a transcriptional repressor, most likely Tup1. The mechanisms responsible for the high level of resistance to caspofungin and fluconazole observed resulting from RCA1 deletion were investigated. From our observations, we propose that caspofungin resistance was the consequence of the deregulation of cell wall gene expression and that fluconazole resistance was linked to the modulation of the cAMP/PKA signaling pathwa...Continue Reading

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Citations

May 1, 2013·Antimicrobial Agents and Chemotherapy·Jamel EddouziDominique Sanglard
Dec 5, 2012·Antimicrobial Agents and Chemotherapy·Luis Vale SilvaDominique Sanglard
Nov 13, 2012·Eukaryotic Cell·Claudia Jiménez-LópezMichael C Lorenz
Apr 16, 2014·PloS One·Xiaojiang TanEleftherios Mylonakis
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Feb 27, 2015·Frontiers in Microbiology·Verónica UrrialdeRebeca Alonso-Monge
Mar 1, 2018·Frontiers in Medicine·Mafalda Cavalheiro, Miguel Cacho Teixeira
Nov 18, 2016·F1000Research·Adnane Sellam, Malcolm Whiteway
Apr 1, 2020·Journal of Fungi·Julia R KöhlerWanjun Qi
Nov 5, 2016·Frontiers in Cellular and Infection Microbiology·Pedro PaisMiguel C Teixeira
Oct 25, 2017·Frontiers in Microbiology·Julien ChaillotAdnane Sellam
Jan 26, 2020·FEMS Yeast Research·Sonia VillaShankar Thangamani
Jun 13, 2019·MSystems·Daniel Zamith-MirandaJoshua D Nosanchuk
Jan 12, 2021·Frontiers in Cellular and Infection Microbiology·Diana L RodriguezClarissa J Nobile
Dec 3, 2020·Frontiers in Microbiology·Carmen Rodríguez-CerdeiraJosé Luís González-Cespón
Feb 16, 2021·Critical Reviews in Microbiology·Hui LuYuanying Jiang

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