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

BMC Genomics

Research Article

Gaelle Lelandais¹  Stéphane Le Crom²  Maria Bernard²  Sophie Lemoine²  Odile Sismeiro³  Jean-Yves Coppée³  Rajendra Prasad⁴  Sanjiveeni Dhamgaye⁴  Frédéric Devaux⁵ 

[1] Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), INTS, Université Paris Diderot, Sorbonne Paris Cité, INSERM, U665, Paris, France;Ecole Normale Supérieure, Institut de Biologie de l´ENS, IBENS, F-75005, Paris, France;Inserm, U1024, F-75005, Paris, France;CNRS, UMR 8197, F-75005, Paris, France;Institut Pasteur, Plate forme Transcriptome et Epigenome, Departement Genomes et Genetique, Paris, France;Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, 110067, New Delhi, India;UPMC, UMR7238, Génomique des Microorganismes, 15 rue de l'École de Médecine, 75006, Paris, France;CNRS, UMR7238, Génomique des Microorganismes, Paris, France;

关键词: Candida albicans;    Multidrug resistance;    Yeast;    RNA-seq;    CZF1;   

DOI  :  10.1186/1471-2164-13-396

 received in 2012-05-25, accepted in 2012-08-03,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundDrug 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.ResultsRNA-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.ConclusionOur 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.

【 授权许可】

Unknown   
© Dhamgaye et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.