P348 tRNA modifications in Candida virulence. (20th September 2022)

• Record Type: Journal Article
• Authors: Böttcher, Bettina; Leidel, Sebastian; Brunke, Sascha
• Is Part Of: Medical mycology. Volume 60(2022)supplement 1
• Publication Date: 2022-09-20
• Subjects: Medical mycology -- Periodicals; Veterinary mycology -- Periodicals; Mycology -- Periodicals; Mycoses -- Periodicals; Pathogenic fungi -- Periodicals; 616.969005
• DOI: 10.1093/mmy/myac072.P348
• Languages: English
• ISSNs: 1369-3786

Abstract

Abstract: Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Candida albicans is a normal commensal of the gastrointestinal tract, but also an important opportunistic pathogen that can cause life-threatening infections. An important pathogenicity factor of C. albicans is its ability to form hyphae, which are associated with the expression of many different virulence factors. The regulation of hypha formation has been analyzed extensively on the transcriptional and also post-translational level in the past. Candida albicans has a closely related sister species, C. dubliniensis, which has a lower propensity to form hyphae and only very rarely causes more than superficial infections. We investigated the differences in the genetic setup of these two species and found a gene whose Saccharomyces cerevisiae homolog is involved in tRNA modifications. We here show that this gene, Hma1, acts as a tRNA-threonyl carbamoyl adenosine dehydratase in C. albicans, and that its activity differs between C. albicans and C. dubliniensis . A deletion mutant shows specific defects in hyphae formation, invasion of host cells, and in virulence in C. albicans . Furthermore, we find that the loss of this tRNA-modifying enzyme leads to changes in ribosome occupancy at 37°C, the temperature encountered in the host. With these data we link tRNA modifications to host-induced processes of one of the most important fungal pathogens of humans. We thereby add another layer of regulation, between transcription and post-translational modifications, to the virulence program of Candida yeasts.