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Series GSE148749 Query DataSets for GSE148749
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
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.
Overall design Method: polyA selection of mRNA from treated and untreated Candida auris, sequenced on a NovaSeq 6000
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
Department Center for Cancer Research
Street address 201 S. University St
City West Lafayette
State/province IN
ZIP/Postal code 47907
Country USA
Platforms (1)
GPL28368 Illumina NovaSeq 6000 ([Candida] auris)
Samples (4)
GSM4478255 whole cells, APR
GSM4478256 whole cells, ITC
GSM4478257 whole cells, ITC_APR
BioProject PRJNA625552
SRA SRP256498

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Supplementary file Size Download File type/resource
GSE148749_APR.RNAseq.genecounts.txt.gz 126.2 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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