Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles

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Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles

Fungi transcriptionally upregulate expression of azole efflux pumps and ergosterol biosynthesis pathway genes when exposed to antifungal agents that target ergosterol biosynthesis. To date, these transcriptional responses have been shown to be dependent on the presence of the azoles and/or depletion of ergosterol. Using an inducible promoter to regulate Neurospora crassa erg11, which encodes th...

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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 dir...

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Many antifungal drugs including the highly successful azoles target the fungal-specific sterol, ergosterol, yet the molecular identity of cellular pathways mediating antifungal activity remained obscure. A recent study on the requirement of ergosterol in vacuolar H+-ATPase (V-ATPase) function uncovered a critical role for ion homeostasis downstream of azole inhibition of ergosterol biosynthesis...

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Antifungal azoles: old and new.

Management of fungal infections is complex with increasing choice of antifungals. Mortality and morbidity are significant despite treatment. Azoles are commonly used compounds which inhibit fungal lanosterol 14 demethylase, thereby depleting ergosterol in the fungal cell membrane with the accumulation of lanosterol precursors. Imidazoles (miconazole, ketoconazole, clotrimazole) are used in topi...

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ژورنال

عنوان ژورنال: Frontiers in Microbiology

سال: 2018

ISSN: 1664-302X

DOI: 10.3389/fmicb.2018.00009