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The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans

Candida albicans is a leading cause of fungal infections in immunocompromised patients. Management of candidemia relies on a few antifungal agents, with fluconazole being first line therapy. The emergence of fluconazole-resistant strains highlights the pressing need to improve our molecular understa...

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Published in:Scientific reports 2024-11, Vol.14 (1), p.29012-10, Article 29012
Main Authors: Stevens, Irene, Silao, Fitz Gerald, Huch, Susanne, Liu, Honglian, Ryman, Kicki, Carvajal-Jimenez, Adriana, Ljungdahl, Per O., Pelechano, Vicent
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creator Stevens, Irene
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description Candida albicans is a leading cause of fungal infections in immunocompromised patients. Management of candidemia relies on a few antifungal agents, with fluconazole being first line therapy. The emergence of fluconazole-resistant strains highlights the pressing need to improve our molecular understanding of the drug response mechanisms. By sequencing the 5’P mRNA degradation intermediates, we establish that co-translational mRNA decay occurs in C. albicans and characterize how in vivo 5´-3´ exonuclease degradation trails the last translating ribosome. Thus, the study of the 5’ Phosphorylated mRNA degradome (5PSeq) offers a simple and affordable way to measure ribosome dynamics and identify codon specific ribosome stalls in response to drugs and amino acid deprivation. Building upon this, we combine RNA-Seq and 5PSeq to study the early response of sensitive and resistant C. albicans isolates to fluconazole. Our results highlight that transcriptional responses, rather than changes in ribosome dynamics, are the main driver of Candida resistance to fluconazole.
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subjects 631/1647/514/1949
631/326/193/2541
631/326/421
631/337/1645/2020
631/337/2019
Amino acids
Antifungal agents
Antifungal Agents - pharmacology
Candida albicans
Candida albicans - drug effects
Candida albicans - genetics
Candidemia
Drug Resistance, Fungal - genetics
Exonuclease
Fluconazole
Fluconazole - pharmacology
Gene Expression Regulation, Fungal - drug effects
Humanities and Social Sciences
Humans
Immunocompromised hosts
Intermediates
Microbial Sensitivity Tests
mRNA turnover
multidisciplinary
Post-transcription
Ribonucleic acid
Ribosomes - drug effects
Ribosomes - metabolism
RNA
RNA Stability - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
Transcription, Genetic - drug effects
title The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans
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