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RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans
- Source :
- BMC Genomics, BMC Genomics, BioMed Central, 2012, 13 (1), pp.396. ⟨10.1186/1471-2164-13-396⟩, BMC Genomics, 2012, 13 (1), pp.396. ⟨10.1186/1471-2164-13-396⟩, BMC Genomics, Vol 13, Iss 1, p 396 (2012)
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 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.
- Subjects :
- Candida albicans
beta-Glucans
lcsh:QH426-470
lcsh:Biotechnology
Repressor
RNA-Seq
Drug resistance
Multidrug resistance
Fungal Proteins
03 medical and health sciences
Drug Resistance, Fungal
lcsh:TP248.13-248.65
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Transcriptional regulation
Genetics
CZF1
Gene
030304 developmental biology
0303 health sciences
biology
030306 microbiology
Sequence Analysis, RNA
Gene Expression Profiling
biology.organism_classification
Yeast
3. Good health
Multiple drug resistance
Gene expression profiling
lcsh:Genetics
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
RNA-seq
Biotechnology
Transcription Factors
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 14712164
- Database :
- OpenAIRE
- Journal :
- BMC Genomics, BMC Genomics, BioMed Central, 2012, 13 (1), pp.396. ⟨10.1186/1471-2164-13-396⟩, BMC Genomics, 2012, 13 (1), pp.396. ⟨10.1186/1471-2164-13-396⟩, BMC Genomics, Vol 13, Iss 1, p 396 (2012)
- Accession number :
- edsair.doi.dedup.....f33f90b7fe603ba7ed13ad32fc065498