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|Title:||Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source|
Kastora, Stavroula L.
Azevedo, Nuno Miguel Morais
Rodrigues, Célia F.
Silva, Sónia Carina
Van Dijck, Patrick
Brown, Alistair J. P.
|Journal:||npj Biofilms and Microbiomes|
|Citation:||Alves, R.; Kastora, Stavroula L.; Gomes-Gonçalves, Alexandra; Azevedo, N.; Rodrigues, Célia F.; Silva, Sónia Carina; Demuyser, Liesbeth; Van Dijck, Patrick; Casal, Margarida; Brown, Alistair J. P.; Henriques, Mariana; Paiva, Sandra, Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source. npj Biofilms and Microbiomes, 6(4), 4, 2020|
|Abstract(s):||Candida glabrata is an important human fungal pathogen known to trigger serious infections in immune-compromised individuals. Its ability to form biofilms, which exhibit high tolerance to antifungal treatments, has been considered as an important virulence factor. However, the mechanisms involving antifungal resistance in biofilms and the impact of host niche environments on these processes are still poorly defined. In this study, we performed a whole-transcriptome analysis of C. glabrata biofilm cells exposed to different environmental conditions and constraints in order to identify the molecular pathways involved in fluconazole resistance and understand how acidic pH niches, associated with the presence of acetic acid, are able to modulate these responses. We show that fluconazole treatment induces gene expression reprogramming in a carbon source and pH-dependent manner. This is particularly relevant for a set of genes involved in DNA replication, ergosterol, and ubiquinone biosynthesis. We also provide additional evidence that the loss of mitochondrial function is associated with fluconazole resistance, independently of the growth condition. Lastly, we propose that C. glabrata Mge1, a cochaperone involved in iron metabolism and protein import into the mitochondria, is a key regulator of fluconazole susceptibility during carbon and pH adaptation by reducing the metabolic flux towards toxic sterol formation. These new findings suggest that different host microenvironments influence directly the physiology of C. glabrata, with implications on how this pathogen responds to antifungal treatment. Our analyses identify several pathways that can be targeted and will potentially prove to be useful for developing new antifungals to treat biofilm-based infections.|
|Description:||The datasets generated in this study are available at public repositories or from the corresponding author upon request. The raw RNA-seq data in fastq format, as well as the processed data have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession number GSE121074.|
|Appears in Collections:||CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series|