The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-80435-w |
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| author | Irene Stevens Fitz Gerald Silao Susanne Huch Honglian Liu Kicki Ryman Adriana Carvajal-Jimenez Per O. Ljungdahl Vicent Pelechano |
| author_facet | Irene Stevens Fitz Gerald Silao Susanne Huch Honglian Liu Kicki Ryman Adriana Carvajal-Jimenez Per O. Ljungdahl Vicent Pelechano |
| author_sort | Irene Stevens |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a416378a8c954ddcb8bccd8e9940aa4b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a416378a8c954ddcb8bccd8e9940aa4b2024-11-24T12:27:03ZengNature PortfolioScientific Reports2045-23222024-11-0114111010.1038/s41598-024-80435-wThe early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicansIrene Stevens0Fitz Gerald Silao1Susanne Huch2Honglian Liu3Kicki Ryman4Adriana Carvajal-Jimenez5Per O. Ljungdahl6Vicent Pelechano7Science for Life Laboratory (SciLifeLab), Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetSciLifeLab, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityScience for Life Laboratory (SciLifeLab), Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetScience for Life Laboratory (SciLifeLab), Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetSciLifeLab, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityScience for Life Laboratory (SciLifeLab), Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetSciLifeLab, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityScience for Life Laboratory (SciLifeLab), Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetAbstract 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.https://doi.org/10.1038/s41598-024-80435-w |
| spellingShingle | Irene Stevens Fitz Gerald Silao Susanne Huch Honglian Liu Kicki Ryman Adriana Carvajal-Jimenez Per O. Ljungdahl Vicent Pelechano The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans Scientific Reports |
| title | The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans |
| title_full | The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans |
| title_fullStr | The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans |
| title_full_unstemmed | The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans |
| title_short | The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans |
| title_sort | early transcriptional and post transcriptional responses to fluconazole in sensitive and resistant candida albicans |
| url | https://doi.org/10.1038/s41598-024-80435-w |
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