Profile of mRNA transcriptomes of E. coli affected by antifungal agent ciclopirox
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ABSTRACT:
PROVIDER: PRJNA434677 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6750910.fastq.gz | Fastqsanger.gz | |||
| SRR6750908.fastq.gz | Fastqsanger.gz | |||
| SRR6750909.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The identification of genes and regulatory pathways involved in the susceptibility to ciclopirox activity Methods: mRNA profiles of ciclopirox treatment in wild-type strain using Illumina sequencing. Results: Using an optimized data analysis workflow, we mapped about 1 million sequence reads per sample to the E. coli K-12 genome and identified 4,290 transcripts in wild-type with our without sublethal concentration of ciclopirox (12.5 ug/mL). Overall, this is the first genome-wide level analysis of ciclopirox as an antibacterial against Gram-negative bacteria and shown that >13 pathways were affected by ciclopirox with the change of expression level of >10 genes. Data analysis with CLRNASeq showed some differently expressed transcripts by ciclopirox treatment. Conclusions: Our study represents the first detailed analysis of ciclopirox-affected transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
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Project description:A 13-(4-isopropylbenzyl)berberine derivative (named KR-72) was synthesized and examined for antifungal activities against various human pathogenic fungi. The synthesized compound exhibited remarkably enhanced antifungal activity than berberine and berberrubine. Regardless of the potent antifungal activity of KR-72, its mode of action and the physiological impacts of the drug on fungal metabolism remain elusive. In this study, we performed the DNA microarray-based transcriptome analysis to identify KR-72 responsive genes and employed reverse genetics approaches to characterize their functions in Cryptococcus neoformans, which causes fatal meningoencephalitis in humans. First, KR-72 treatment altered in remodeling of transcriptome profiles in C. neoformans. Genes involved in translation and transcription were mostly upregulated, while those involved in cytoskeleton, intracellular trafficking, lipid and carbohydrate metabolism and energy production were downregulated. Supporting this, KR-72 has a strong synergistic effect with a calcineurin inhibitor FK506, while it has an antagonistic effect with polyene drug. Finally, KR-72 treatment promoted expression of ECM16, NOP14, HSP10, and MGE1, which we proved to be essential for the growth of C. neoformans. Among them, KR-72 mediated induction of MGE1 also appeared to hamper the viability of C. neoformans, potentially through impaired cell cycle or DNA repair system. This study will proposed mode of action for KR-72.
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