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https://hdl.handle.net/1822/65601
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Campo DC | Valor | Idioma |
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dc.contributor.author | Alves, R. | por |
dc.contributor.author | Kastora, Stavroula L. | por |
dc.contributor.author | Gomes-Gonçalves, Alexandra | por |
dc.contributor.author | Azevedo, Nuno Miguel Morais | por |
dc.contributor.author | Rodrigues, Célia F. | por |
dc.contributor.author | Silva, Sónia Carina | por |
dc.contributor.author | Demuyser, Liesbeth | por |
dc.contributor.author | Van Dijck, Patrick | por |
dc.contributor.author | Casal, Margarida | por |
dc.contributor.author | Brown, Alistair J. P. | por |
dc.contributor.author | Henriques, Mariana | por |
dc.contributor.author | Paiva, Sandra | por |
dc.date.accessioned | 2020-06-09T14:15:38Z | - |
dc.date.available | 2020-06-09T14:15:38Z | - |
dc.date.issued | 2020 | - |
dc.identifier.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 | por |
dc.identifier.uri | https://hdl.handle.net/1822/65601 | - |
dc.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. | por |
dc.description.abstract | 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. | por |
dc.description.sponsorship | This study was supported by the Portuguese National Funding Agency for Science, Research, and Technology FCT (grant PTDC/BIAMIC/5184/2014). R.A. received FCT Ph.D fellowship (PD/BD/113813/2015). We gratefully acknowledge Edinburgh Genomics for RNA-Seq library preparation and sequencing. The work on CBMA was supported by the strategic programs UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) and UID/BIA/04050/2019. The work on CEB was supported by PEst-OE/EQB/LA0023/2013, from FCT, “BioHealth-Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2–O Novo Norte), QREN, FEDER and the project “Consolidating Research Expertize and Resources on Cellular and Molecular Biotechnology at CEB/IBB”, Ref. FCOMP-01-0124-FEDER-027462. The work in Aberdeen was also supported by the European Research Council through the advanced grant “STRIFE” (C-2009-AdG-249793), by the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Center for Medical Mycology and the University of Aberdeen (MR/N006364/1). The work at KU Leuven was supported by the Federation of European Biochemical Societies (FEBS) through a short-term fellowship awarded to R.A. and by the Fund for Scientific Research Flanders (FWO; WO.009.16N). We thank Beatriz Herrera-Malaver for technical assistance with the GC-MS analysis. | por |
dc.language.iso | eng | por |
dc.publisher | Nature Research | por |
dc.relation | PTDC/BIAMIC/5184/2014 | por |
dc.relation | PD/BD/113813/2015 | por |
dc.relation | info:eu-repo/grantAgreement/FCT/5876/147364/PT | por |
dc.relation | UID/BIA/04050/2019 | por |
dc.relation | info:eu-repo/grantAgreement/FCT/3599-PPCDT/132966/PT | por |
dc.rights | openAccess | por |
dc.subject | Antimicrobials | por |
dc.subject | Biofilms | por |
dc.subject | Cellular microbiology | por |
dc.subject | Next-generation sequencing | por |
dc.subject | Pathogensv | por |
dc.title | Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source | por |
dc.type | article | - |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | http://www.nature.com/npjbiofilms/ | por |
dc.comments | CEB53434 | por |
oaire.citationIssue | 1 | por |
oaire.citationVolume | 6 | por |
dc.date.updated | 2020-01-26T10:25:12Z | - |
dc.identifier.eissn | 2055-5008 | por |
dc.identifier.doi | 10.1038/s41522-020-0114-5 | por |
dc.identifier.pmid | 31993211 | por |
dc.description.publicationversion | info:eu-repo/semantics/publishedVersion | - |
dc.subject.wos | Science & Technology | por |
sdum.journal | npj Biofilms and Microbiomes | por |
oaire.version | VoR | por |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_53434_1.pdf | 2,81 MB | Adobe PDF | Ver/Abrir |