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


CONCLUSIONS
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.
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Sanjiveeni
S
Dhamgaye
Maria
M
Bernard
Gaelle
G
Lelandais
Odile
O
Sismeiro
Sophie
S
Lemoine
Jean-Yves
JY
Coppée
Stéphane
S
Le Crom
Rajendra
R
Prasad
Frédéric
F
Devaux
D002176:Candida albicans / Q000235:genetics*; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D047071:beta-Glucans / Q000378:metabolism
D005656:Fungal Proteins; D014157:Transcription Factors; D047071:beta-Glucans; C077336:CZF1 protein, Candida albicans