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| Status |
Public on Apr 04, 2024 |
| Title |
A highly conserved tRNA modification contributes to C. albicans filamentation and virulence |
| Organism |
Candida albicans |
| Experiment type |
Other
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| Summary |
tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker’s yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic Candida albicans and its much less pathogenic sister species, Candida dubliniensis, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits speciesspecific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C—the body temperature of the human host. A C. albicans HMA1 deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.
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| Overall design |
Candida albicans wild type and hma1 knockout strains were grown at 30°C and 37°C and analyzed by ribosome profiling to study the role of ct6A in translation.
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| Web link |
https://journals.asm.org/doi/10.1128/spectrum.04255-22
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| Contributor(s) |
Böttcher B, Kienast SD, Leufken J, Eggers C, Sharma P, Leufken C, Morgner B, Schulz D, Drexler HA, Allert S, Jacobsen ID, Vylkova S, Leidel SA, Brunke S |
| Citation(s) |
38587411 |
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| Submission date |
Mar 25, 2022 |
| Last update date |
Jul 05, 2024 |
| Contact name |
Sebastian Andreas Leidel |
| E-mail(s) |
sebastian.leidel@unibe.ch
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| Phone |
+41 31 631 42 96
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| Organization name |
University of Bern
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| Department |
Department of Chemistry and Biochemistry
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| Lab |
Research group for RNA Biochemistry
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| Street address |
Freiestrasse 3
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| City |
Bern |
| State/province |
Bern |
| ZIP/Postal code |
3012 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL22403 |
Illumina NextSeq 500 (Candida albicans) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA819979 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199421_CanAlb_HMA1_KO_and_WT_raw_counts.txt.gz |
152.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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