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Status |
Public on Aug 05, 2023 |
Title |
Genome-wide Translational Response of Candida albicans to Fluconazole Treatment |
Organism |
Candida albicans |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Azoles are commonly used for the treatment of fungal infections and the ability of human fungal pathogens to rapidly respond to azole treatment is critical for the development of antifungal resistance. While the role of genetic mutations, chromosomal rearrangements and transcriptional mechanisms in azole resistance has been well-characterized, very little is known about post-transcriptional and translation mechanisms that drive this process. In addition, most previous genome-wide studies have focused on transcriptional responses to azole treatment, and likely serve as an inaccurate proxies due to extensive post-transcriptional and translational regulation. In this study we use ribosome profiling to provide the first picture of the global translational response of a major human fungal pathogen, Candida albicans, to treatment with fluconazole, one of the most widely used azole drugs. We identify sets of genes showing significantly altered translational efficiency (TE), including genes associated with a variety of biological processes such as the cell cycle, DNA repair, cell wall/cell membrane biosynthesis, transport, signaling, DNA- and RNA-binding activities and protein synthesis. Importantly, while there are similarities and differences among gene categories that are regulated by fluconazole at the translational vs. transcriptional levels, we observe very little overlap among individual genes controlled by these mechanisms. Our findings suggest that C. albicans possesses distinct translational mechanisms that are important for the response to antifungal treatment, which could eventually be targeted by novel antifungal therapies.
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Overall design |
Examination of gene expression by RNA-seq and Ribo-seq in 1 strain of Candida albicans grown under 2 conditions (YEPD + 1 ug/mL fluconazole at 30°C (Fluconazole)) and (YEPD + DMSO vehicle only control at 30°C (No drug)). There are four biological replicates for each strain grown under each condition (16 samples total).
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Contributor(s) |
Kadosh D, Choudhary S |
Citation(s) |
37610232 |
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Submission date |
Mar 17, 2023 |
Last update date |
Oct 26, 2023 |
Contact name |
David Kadosh |
E-mail(s) |
kadosh@uthscsa.edu
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Phone |
(210) 567-3976
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Organization name |
University of Texas Health Science Center at San Antonio
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Department |
Department of Microbiology, Immunology & Molecular Genetics
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Street address |
7703 Floyd Curl Dr., MC: 7758
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City |
San Antonio |
State/province |
Texas |
ZIP/Postal code |
78229 |
Country |
USA |
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Platforms (1) |
GPL27827 |
Illumina HiSeq 3000 (Candida albicans) |
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Samples (16)
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Relations |
BioProject |
PRJNA945876 |
Supplementary file |
Size |
Download |
File type/resource |
GSE227590_ribo_rna_counts.tsv.gz |
182.7 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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