iBB

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.

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.

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.