PXD048351 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mod5 mediates a molecular trade-off between optimal gene expression and antifungal resistance |
Description | Increasing antifungal drug resistance is a major concern associated with human fungal infections. Genetic mutation and epimutation mechanisms are clearly linked to resistance in some fungi, but few studies have investigated RNA modifications (the epitranscriptome) as a mediator of resistance. Here, deletion of the Aspergillus fumigatus tRNA-modifying isopentenyl transferase ortholog, Mod5, led to altered growth and stress response, but also unexpected resistance against the antifungal drug 5-fluorocytosine (5-FC). Simultaneous profiling of the transcriptome and proteome of 5-FC-stressed wild-type and ∆mod5 strains revealed a similar general adaptation to stress; however, the knockout displayed elevated expression of cross-pathway control (CPC) genes. Quantification of CPC transcription factor cpcA and client gene argB showed premature CPC activation in ∆mod5, which was further increased upon treatment with 5-FC. By associating codon usage patterns with proteomics abundances, we observed the number of tRNATyrGΨA-decoded codons to negatively correlate with protein abundance in the knockout, indicative of modification-tuneable transcripts. Subsequent overexpression of tRNATyrGΨA in the ∆mod5 strain rescued select phenotypes but, surprisingly, failed to reverse 5-FC resistance. Investigation of the purported tRNA gene-mediated silencing function of Mod5 uncovered a negative correlation between tRNA proximity and gene induction under normal growth, suggesting that tRNA gene-mediated silencing is active in A. fumigatus. In conclusion, 5-FC resistance in the absence of the bifunctional Mod5 protein likely originates from multifaceted transcriptional and translational changes that skew the fungus towards starvation responses over optimal growth, potentially offering a mechanism reliant on RNA modification and tRNA gene-mediated silencing capable of facilitating transient antifungal resistance. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-23 |
AnnouncementXML | Submission_2024-10-23_08:16:33.466.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Thomas Krüger |
SpeciesList | scientific name: Aspergillus fumigatus CEA17; NCBI TaxID: 1266464; |
ModificationList | phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-01-09 07:48:05 | ID requested | |
⏵ 1 | 2024-10-23 08:16:33 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: tRNA modification, Aspergillus fumigatus, antifungal resistance,5-fluorocytosine |
Contact List
Axel A. Brakhage |
contact affiliation | Department for Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena (Leibniz-HKI), Jena, Germany |
contact email | axel.brakhage@leibniz-hki.de |
lab head | |
Thomas Krüger |
contact affiliation | Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute |
contact email | thomas.krueger@leibniz-hki.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD048351
- Label: PRIDE project
- Name: Mod5 mediates a molecular trade-off between optimal gene expression and antifungal resistance