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Mónica da Luz Galocha defended her PhD thesis in Biotechnology and Biosciences, titled “Unveiling new pathways of genomic evolution towards drug resistance in Candida glabrata”, on the 13th of February 2023, at Instituto Superior Técnico. During the previous four years, and under the supervision of Miguel Cacho Teixeira from iBB, Mónica studied the genomic basis of the evolution towards antifungal drug resistance in the fungal pathogen Candida glabrata, uncovering fascinating new mechanisms of azole drug import and transcriptome-wide remodelling in the dependency of mediator complex components.

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.

Mónica Galocha was distinguished with the Best PhD Work in Research and Infectious Diseases by redeSAÚDE, University of Lisbon, at the 6th redeSAÚDE conference held at University of Lisboa on the 15th of November 2022. Mónica Galocha presented her research focused on unveiling new pathways of genomic evolution towards drug resistance in Candida glabrata, carried at iBB, under the supervision of Professor Miguel Cacho Teixeira.

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.