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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 |
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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. |
doi_str_mv | 10.1038/s41598-024-80435-w |
format | article |
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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
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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.</description><subject>631/1647/514/1949</subject><subject>631/326/193/2541</subject><subject>631/326/421</subject><subject>631/337/1645/2020</subject><subject>631/337/2019</subject><subject>Amino acids</subject><subject>Antifungal agents</subject><subject>Antifungal Agents - pharmacology</subject><subject>Candida albicans</subject><subject>Candida albicans - drug effects</subject><subject>Candida albicans - genetics</subject><subject>Candidemia</subject><subject>Drug Resistance, Fungal - genetics</subject><subject>Exonuclease</subject><subject>Fluconazole</subject><subject>Fluconazole - pharmacology</subject><subject>Gene Expression Regulation, Fungal - drug effects</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunocompromised hosts</subject><subject>Intermediates</subject><subject>Microbial Sensitivity Tests</subject><subject>mRNA turnover</subject><subject>multidisciplinary</subject><subject>Post-transcription</subject><subject>Ribonucleic acid</subject><subject>Ribosomes - 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39578617</pmid><doi>10.1038/s41598-024-80435-w</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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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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