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A Neofunctionalized Transcription Factor Controls Azole Resistance in C. glabrata

A Neofunctionalized Transcription Factor Controls Azole Resistance in C. glabrata | iBB | Scoop.it

The prevalence of antifungal resistance in Candida glabrata, especially against azole drugs, results in difficult-to-treat and potentially life-threatening infections. In this study, the role of a newly described transcription factor, Mar1, in azole susceptibility was explored. Using RNA-sequencing, its role in the transcriptome-wide response to fluconazole is assessed, leading to the elucidation of its role in modulating azole susceptibility, dependent on membrane sphingolipid incorporation, membrane permeability, and intracellular drug accumulation. Altogether, a regulatory pathway modulating azole susceptibility in C. glabrata is proposed, resulting from what appears to be a neofunctionalization of a Hap1-like transcription factor. These results obtained by an international team led by Miguel Cacho Teixeira, BSRG-iBB, just published in Journal of Fungi, are expected to contribute to maintain the usability of this drug in antifungal therapy.

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Mónica Galocha Receives Best Poster Award at HFP2019

Mónica Galocha Receives Best Poster Award at HFP2019 | iBB | Scoop.it

Mónica Galocha, PhD student from the PhD program AEM-Applied Environmental Microbiology, won one of the PhD poster prizes awarded at the eight FEBS Advance Lecture Course on Human Fungal Pathogens-Molecular Mechanisms of Host-Pathogen Interactions and Virulence, held on May 18-24, in La Colle sur Loup, France, with a communication entitled “Candida glabrata evolution towards posaconazole resistance irrespective of PDR1 GOF mutations”. The work results from a collaboration between researchers from BSRG-iBB (Miguel Cacho Teixeira), University of Porto (Acácio G. Rodrigues) and Chiba University (Hiroji Chibana).

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New Pathway Controlling Azole Resistance in Candida glabrata

New Pathway Controlling Azole Resistance in Candida glabrata | iBB | Scoop.it

The ability to acquire azole resistance is an emblematic trait of the fungal pathogen Candida glabrata. Understanding the molecular basis of azole resistance in this pathogen is crucial to design more suitable therapeutic strategies. In this study, the transcription factor Rpn4 was found to play a key role in the transcriptome-wide response to fluconazole. Rpn4 is described a new regulator of the ergosterol biosynthesis pathway in C. glabrata, contributing to plasma membrane homeostasis, decreasing azole drug accumulation and, thus, conferring azole resistance. These results  obtained by an international team led by Miguel Cacho Teixeira, BSRG-iBB, just published in Antimicrobial Agents and Chemotherapy, are expected to contribute to maintain the usability of this drug in antifungal therapy.

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