Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans

Sanjiveeni Dhamgaye1, Maria Bernard345, Gaelle Lelandais6, Odile Sismeiro7, Sophie Lemoine345, Jean-Yves Coppée7, Stéphane Le Crom345, Rajendra Prasad1* and Frédéric Devaux28

Author Affiliations

1 Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India

2 UPMC, UMR7238, Génomique des Microorganismes, 15 rue de l'École de Médecine, 75006, Paris, France

3 Ecole Normale Supérieure, Institut de Biologie de l´ENS, IBENS, Paris, F-75005, France

4 Inserm, U1024, Paris, F-75005, France

5 CNRS, UMR 8197, Paris, F-75005, France

6 Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), INTS, Université Paris Diderot, Sorbonne Paris Cité, INSERM, U665, Paris, France

7 Institut Pasteur, Plate forme Transcriptome et Epigenome, Departement Genomes et Genetique, Paris, France

8 CNRS, UMR7238, Génomique des Microorganismes, Paris, France

For all author emails, please log on.

BMC Genomics 2012, 13:396  doi:10.1186/1471-2164-13-396

Published: 16 August 2012

Abstract

Background

Drug susceptible clinical isolates of Candida albicans frequently become highly tolerant to drugs during chemotherapy, with dreadful consequences to patient health. We used RNA sequencing (RNA-seq) to analyze the transcriptomes of a CDR (Candida Drug Resistance) strain and its isogenic drug sensitive counterpart.

Results

RNA-seq unveiled differential expression of 228 genes including a) genes previously identified as involved in CDR, b) genes not previously associated to the CDR phenotype, and c) novel transcripts whose function as a gene is uncharacterized. In particular, we show for the first time that CDR acquisition is correlated with an overexpression of the transcription factor encoding gene CZF1. CZF1 null mutants were susceptible to many drugs, independently of known multidrug resistance mechanisms. We show that CZF1 acts as a repressor of β-glucan synthesis, thus negatively regulating cell wall integrity. Finally, our RNA-seq data allowed us to identify a new transcribed region, upstream of the TAC1 gene, which encodes the major CDR transcriptional regulator.

Conclusion

Our results open new perspectives of the role of Czf1 and of our understanding of the transcriptional and post-transcriptional mechanisms that lead to the acquisition of drug resistance in C. albicans, with potential for future improvements of therapeutic strategies.

Keywords:
Candida albicans; Multidrug resistance; Yeast; RNA-seq; CZF1