sirolimus has been researched along with Cryptococcosis* in 3 studies
3 other study(ies) available for sirolimus and Cryptococcosis
| Article | Year |
|---|---|
Effect of rapamycin on
Cryptococcosis is a fungal infection caused by a type of fungus called Topics: Cryptococcosis; Cryptococcus neoformans; Humans; Sirolimus; Virulence; Virulence Factors | 2023 |
Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans.
Cryptococcus neoformans infections cause approximately 15% of AIDS-related deaths owing to a combination of limited antifungal therapies and drug resistance. A collection of clinical and environmental C. neoformans isolates were assayed for increased mutation rates via fluctuation analysis, and we identified two hypermutator C. neoformans clinical isolates with increased mutation rates when exposed to the combination of rapamycin and FK506. Sequencing of drug target genes found that Cnl1 transposon insertions conferred the majority of resistance to rapamycin and FK506 and could also independently cause resistance to 5-fluoroorotic acid and the clinically relevant antifungal 5-flucytosine. Whole-genome sequencing revealed both hypermutator genomes harbour a nonsense mutation in the RNA-interference component ZNF3 and hundreds of Cnl1 elements organized into massive subtelomeric arrays on each of the fourteen chromosomes. Quantitative trait locus mapping in 28 progeny derived from a cross between a hypermutator and wild-type identified a locus associated with hypermutation that included znf3. CRISPR editing of the znf3 nonsense mutation abolished hypermutation and restored small-interfering-RNA production. We conclude that hypermutation and drug resistance in these clinical isolates result from RNA-interference loss and accumulation of Cnl1 elements. Topics: Antifungal Agents; Codon, Nonsense; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Humans; RNA Interference; Sirolimus; Tacrolimus | 2022 |
The Cryptococcus neoformans Flc1 Homologue Controls Calcium Homeostasis and Confers Fungal Pathogenicity in the Infected Hosts.
Cryptococcus neoformans, an opportunistic yeast pathogen, relies on a complex network of stress response pathways that allow for proliferation in the host. In Saccharomyces cerevisiae, stress responses are regulated by integral membrane proteins containing a transient receptor potential (TRP) domain, including the flavin carrier protein 1 (Flc1), which regulates calcium homeostasis and flavin transport. Here, we report that deletion of C. neoformans Topics: Animals; Antifungal Agents; Calcineurin; Calcium; Carrier Proteins; Chitin; Cryptococcosis; Cryptococcus neoformans; Cyclosporine; Flavins; Fungal Proteins; Homeostasis; Humans; Mechanistic Target of Rapamycin Complex 1; Membrane Proteins; Mice; Saccharomyces cerevisiae; Sirolimus; Transcription Factors; Virulence | 2022 |