RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicansReportar como inadecuado

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BMC Genomics

, 13:396

Eukaryote microbial genomics


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.

KeywordsCandida albicans Multidrug resistance Yeast RNA-seq CZF1 Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-13-396 contains supplementary material, which is available to authorized users.

Rajendra Prasad and Frédéric Devaux contributed equally to this work.

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Autor: Sanjiveeni Dhamgaye - Maria Bernard - Gaelle Lelandais - Odile Sismeiro - Sophie Lemoine - Jean-Yves Coppée - Stéphane Le

Fuente: https://link.springer.com/

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