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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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BIOTECnico PhD Alumni Seminar: Pedro Pais

BIOTECnico PhD Alumni Seminar: Pedro Pais | iBB | Scoop.it

Pedro Pais will be giving a talk entitled "Unveiling the complex regulatory network governing antifungal drug resistance in Candida glabrata: from new regulators to new effectors", Tuesday the 16th february at 16:00 h via zoom. Pedro obtained his PhD in Biotechnology and Biosciences in 2019 and is currently an Assistant Researcher at iBB.

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Pedro Pais to Defend PhD Thesis in Biotechnology and Biosciences

Pedro Pais to Defend PhD Thesis in Biotechnology and Biosciences | iBB | Scoop.it

Pedro Henrique Magalhães Fernandes Pais will be defending his PhD thesis in Biotechnology and Biosciences at Instituto Superior Técnico, friday the 27th september 2019 (10:00 H, room PA-3). During the last years, and under the supervision of Miguel Teixeira from BSRG-iBB, Pedro studied the intricacies of the regulatory network that controls drug resistance in the fungus Candida glabrata. The title of his thesis is "Unveiling the complex regulatory network governing antifungal drug resistance in Candida glabrata: from new regulators to new effectors".

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BIOTECnico Student Pedro Pais Shares Results on Antifungal Antibiotic Resistance

BIOTECnico Student Pedro Pais Shares Results on Antifungal Antibiotic Resistance | iBB | Scoop.it
Pedro Pais, a 2nd year student of the BIOTECnico PhD Program presents highlights of his project on Drug Resistance in Candida Glabrata during the 2nd joint BIOTECnico and AEM PhD Programs workshop that took place at Instituto Superior Técnico on the 15th and 16th February.
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Controlling Biofilm Establishment Since the First Touch

Controlling Biofilm Establishment Since the First Touch | iBB | Scoop.it

Candida glabrata’s ability to cause human infections is tightly linked to its impressive ability to form persistent biofilms. The molecular control of this process is far from being clarified, as it lacks many of the typical features displayed by other Candida species. In this study, a combination of genetic screening, RNA-seq based transcriptomics, and Single-Cell Force Spectroscopy (SCFS), enabled the observation that the transcription factor CgEfg1, but not CgTec1, is necessary for the initial interaction of C. glabrata cells with both abiotic surfaces used in medical devices and epithelial cells, while both transcription factors orchestrate biofilm maturation. The knowledge gathered through this study by former PhD student Mafalda Cavalheiro, and an international team led by Miguel Cacho Teixeira, BSRG-iBB, including Etienne Dague, LAAS-CNRS, Geraldine Butler, University College Dublin, and Arsénio Fialho, BSRG-iBB, and just published in Communications Biology, is expected to contribute to guide the design of more successful therapeutic approaches.

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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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Following the Evolution Towards Fluconazole Resistance in C. glabrata

Following the Evolution Towards Fluconazole Resistance in C. glabrata | iBB | Scoop.it

The effectiveness of Candida glabrata as an emerging human pathogen relies on its ability to acquire azole drug resistance. In a paper just published in Antimicrobial Agents and Chemotherapy, the first time-course evaluation of the global gene expression changes that lead a drug susceptible C. glabrata clinical isolate to step-wise acquisition of resistance to azole drugs was conducted. This work, which results from the collaboration of six different teams under the coordination of Miguel C Teixeira from BSRG-iBB, highlights the multifactorial nature of azole resistance acquisition, including the Epa3 adhesin as a new player, while providing fascinating clues on the underlying evolutionary path. This knowledge is of crucial importance to design more effective antifungal therapy.

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