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| Status |
Public on Oct 19, 2020 |
| Title |
Aprepitant, an antiemetic agent, displays potent synergistic interactions with azole drugs against emerging multidrug-resistant Candida auris |
| Organism |
[Candida] auris |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Combination therapies can be a promising tool to augment the antifungal activity of azole drugs against resistant Candida species. Here, we report the interaction between aprepitant, an antiemetic agent, and azole drugs against different Candida species including the emerging multidrug-resistant C. auris. Particularly, aprepitant enhanced the antifungal activity of itraconazole against C. auris by reducing its minimum inhibitory concentration (MIC) by 2-8 folds. Using Caenorhabditis elegans as an in vivo infection model, the aprepitant/itraconazole combination significantly prolonged the survival of the infected nematodes by ~90% and reduced the fungal burden by ~92% relative to the untreated control. Interestingly, the aprepitant/itraconazole combination exerted a potent fungicidal activity against both planktonic and adherent C. auris biofilms. Further, aprepitant/itraconazole displayed broad-spectrum synergistic interactions against other medically important Candida species including C. albicans, C. krusie, C. tropicalis, and C. parapsilosis (ƩFICI ranged from 0.08 to 031). Comparative transcriptomic profiling indicated aprepitant/itraconazole interferes significantly with metal ions homeostasis and compromises the ROS (reactive oxygen species) detoxification ability of C. auris. This study presents aprepitant as a novel, potent and broad-spectrum azole chemosensitizing agent that warrants further investigation.
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| Overall design |
Method: polyA selection of mRNA from treated and untreated Candida auris, sequenced on a NovaSeq 6000
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| Contributor(s) |
Eldesouky HE, Lanman NA, Hazbun TR, Seleem MN |
| Citation(s) |
33100149 |
| Submission date |
Apr 15, 2020 |
| Last update date |
Nov 09, 2020 |
| Contact name |
Nadia Marie Atallah |
| Organization name |
Purdue University
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| Department |
Center for Cancer Research
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| Street address |
201 S. University St
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| City |
West Lafayette |
| State/province |
IN |
| ZIP/Postal code |
47907 |
| Country |
USA |
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| Platforms (1) |
| GPL28368 |
Illumina NovaSeq 6000 ([Candida] auris) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA625552 |
| SRA |
SRP256498 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148749_APR.RNAseq.genecounts.txt.gz |
126.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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