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The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0002-4350-8395
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Number of Authors: 82024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 29012Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2024. Vol. 14, no 1, article id 29012
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Immunology in the Medical Area
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URN: urn:nbn:se:su:diva-240803DOI: 10.1038/s41598-024-80435-wISI: 001362462000024PubMedID: 39578617Scopus ID: 2-s2.0-85209729348OAI: oai:DiVA.org:su-240803DiVA, id: diva2:1946142
Available from: 2025-03-20 Created: 2025-03-20 Last updated: 2025-03-20Bibliographically approved

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Silao, Fitz-Gerald S.Ryman, KickiLjungdahl, Per

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