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

TitleRNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans.
Publication TypeJournal Article
Year of Publication2012
AuthorsDhamgaye, S, Bernard, M, Lelandais, G, Sismeiro, O, Lemoine, S, Coppée, J-Y, Le Crom, S, Prasad, R, Devaux, F
JournalBMC Genomics
Date Published2012
Keywordsbeta-Glucans, Candida albicans, Drug Resistance, Fungal, Fungal Proteins, Gene Expression Profiling, Sequence Analysis, RNA, Transcription Factors

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.

Alternate JournalBMC Genomics
PubMed ID22897889
PubMed Central IDPMC3447688

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