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Series GSE267057 Query DataSets for GSE267057
Status Public on May 13, 2024
Title Small molecule inhibitors of fungal ∆(9) fatty acid desaturase as antifungal agent against Candida auris
Organisms Candida albicans SC5314; Candidozyma auris
Experiment type Expression profiling by high throughput sequencing
Other
Summary Candida auris has emerged as a significant healthcare-associated pathogen, posing a serious challenge due to its multidrug-resistant nature. Given the pre-existing constraints in the discovery and provision of new antifungals, there is thus an urgent imperative to design effective strategies to tackle this pressing global concern. Here, we screened a chemical library and identified phenyl-carbohydrazide derivatives with potent activity against both C. auris and the most prevalent human fungal pathogen, C. albicans. SPB00525 (N'-(2,6-Dichlorophenyl)-5-nitro-2-furohydrazide) exhibited potent activity against different strains that were resistant to standard antifungals. Using drug-induced haploinsufficient profiling, transcriptomics and metabolomic analysis, we uncovered that Ole1, a ∆(9) fatty acid desaturase, is most likely the target of SPB00525. We also found that another SPB00525 analog, HTS06170 (N'-(2,6-Dichlorophenyl)-4-methyl-1,2,3-thiadiazole-5-carbohydrazide) had a superior antifungal activity against both C. auris and C. albicans. Both SPB00525 and HTS06170 act as antivirulence agents and inhibited the invasive hyphal growth and biofilm formation of C. albicans. SPB00525 and HTS06170 attenuated fungal damage to human enterocytes and ameliorate survival of Galleria mellonella larvae used as a model of systemic candidiasis. These data, suggest that inhibiting ∆(9) fatty acid desaturase activity represents a potential therapeutic approach for treating fungal infection caused by the superbug C. auris and the most prevalent human fungal pathogen, C. albicans.
 
Overall design In this study, we used RNA-seq to identify transcripts modulated by exposure to a novel antifungal molecule (SPB00525) in two human fungal pathogens: Candida auris and C. albicans. We also used drug-induced haploinsufficient profiling to capture the potential target(s) of SPB00525.
Web link https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1434939/full
 
Contributor(s) Sellam A, Tebbji F, Menon AC, Khemiri I, St-Cyr D, Vincent AT
Citation(s) 39282497
Submission date May 08, 2024
Last update date Sep 19, 2024
Contact name Adnane Sellam
E-mail(s) adnane.sellam@gmail.com
Organization name University Laval
Street address 2705 Laurier Blvd.
City Quebec city
ZIP/Postal code G1V 4G2
Country Canada
 
Platforms (3)
GPL28368 Illumina NovaSeq 6000 ([Candida] auris)
GPL33190 Illumina NovaSeq 6000 (Candida albicans SC5314)
GPL34459 Illumina MiSeq (Candida albicans SC5314)
Samples (24)
GSM8259063 C. albicans_15min_Control_R1
GSM8259064 C. albicans_15min_Control_R2
GSM8259065 C. albicans_15min_SPB00525 _R1
Relations
BioProject PRJNA1109421

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE267057_Mutant_fitness_scores.txt.gz 71.4 Kb (ftp)(http) TXT
GSE267057_raw_counts_SPB00525_C.albicans.txt.gz 199.5 Kb (ftp)(http) TXT
GSE267057_raw_counts_SPB00525_C.auris.txt.gz 179.2 Kb (ftp)(http) TXT
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Raw data are available in SRA

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