De-repression of CSP-1 activates adaptive responses to antifungal azoles

Scientific Reports
Xi ChenShaojie Li

Abstract

Antifungal azoles are the major drugs that are used to treat fungal infections. This study found that in response to antifungal azole stress, Neurospora crassa could activate the transcriptional responses of many genes and increase azole resistance by reducing the level of conidial separation 1 (CSP-1), a global transcription repressor, at azole-responsive genes. The expression of csp-1 was directly activated by the transcription factors WC-1 and WC-2. Upon ketoconazole (KTC) stress, the transcript levels of wc-1 and wc-2 were not changed, but csp-1 transcription rapidly declined. A chromatin immunoprecipitation-quantitative polymerase chain reaction analysis revealed a rapid reduction in the WC-2 enrichment at the csp-1 promoter upon KTC treatment, which might be responsible for the KTC-induced csp-1 downregulation. Deletion of csp-1 increased resistance to KTC and voriconazole, while csp-1 overexpression increased KTC susceptibility. CSP-1 transcriptionally repressed a number of azole-responsive genes, including genes encoding the azole target ERG11, the azole efflux pump CDR4, and the sterol C-22 desaturase ERG5. Deletion of csp-1 also reduced the KTC-induced accumulation of ergosterol intermediates, eburicol, and 14α-methyl...Continue Reading

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Citations

Oct 21, 2016·Frontiers in Microbiology·Xiaokui GuXianyun Sun
Feb 2, 2018·Frontiers in Microbiology·Chengcheng HuShaojie Li
Apr 13, 2018·Microbiology and Molecular Biology Reviews : MMBR·Meritxell RiquelmeReinhard Fischer

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Methods Mentioned

BETA
immunoprecipitation
PCR
ChIP

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