Miguel Teixeira
Ontology highlight
ABSTRACT:
INSTRUMENT(S): TripleTOF 5600
ORGANISM(S): [candida] Glabrata (ncbitaxon:5478)
SUBMITTER: Miguel Teixeira
PROVIDER: MSV000079183 | MassIVE | Mon Jul 06 11:38:00 BST 2015
REPOSITORIES: MassIVE
Similar Datasets
Project description:Membrane proteome-wide response to the antifungal drug clotrimazole in Candida glabrata: role of the transcription factor CgPdr1 and the Drug:H+ Antiporters CgTpo1_1 and CgTpo1_2
2015-08-04 | MSV000079209 | MassIVE
Project description:The frequent use of antifungal agents has contributed to the emergence of previously rare or unidentified drug-resistant fungal species, such as Candida auris, which presents mortality rates exceeding 40% and antifungal resistance rates surpassing 90%. The rise of life-threatening infections caused by these increasingly drug-resistant fungal pathogens, coupled with the limited arsenal of effective antifungal agents, necessitates the urgent development of novel strategies to combat multidrug resistance. In this study, we systematically evaluated the role of post-translational modifications (PTMs) of histone H3 in drug resistance in C. auris, focusing on acetylation mediated by the acetyltransferases Gcn5 and Rtt109, as well as methylation by the methyltransferases Set1, Set2, and Dot1. Mutants deficient in these enzymes exhibited varying degrees of antifungal drug sensitivity. Notably, we discovered that GCN5 depletion and the subsequent loss of histone H3 acetylation downregulate key genes involved in ergosterol biosynthesis and drug efflux, resulting in increased susceptibility to major antifungal classes such as azoles and polyenes. Additionally, Gcn5 regulates cell wall integrity and echinocandin resistance through modulation of the calcineurin signaling pathway and the transcription factor Cas5. In invasive infection models using Galleria mellonella and immunocompromised mice, the deletion of GCN5 significantly reduced the virulence of C. auris. Furthermore, we demonstrated that the Gcn5 inhibitor CPTH2, when combined with the antifungal drug caspofungin (CAS), exhibits a synergistic effect against C. auris in both in vitro and in vivo models without significant toxicity to human cells or mice. In conclusion, these findings highlight the critical role of Gcn5 in the resistance and pathogenicity of C. auris, positioning it as a promising therapeutic target for combating invasive fungal infections.
2025-04-05 | GSE293594 | GEO
Project description:We used whole transcriptome profiling (RNA-seq) to analyze the effects of Cu availability on the transcriptomic response of Candida albicans to the azole antifungal drug fluconazole. This study provides a framework for understanding how two treatments work in concert to generate unique impacts on stress response mechanisms of pathogenic fungi.
2021-01-31 | GSE159545 | GEO
Project description:The leucine CUG codon was reassigned to serine in the fungal pathogen Candida albicans. To clarify the biological role of this tuneable codon ambiguity on drug resistance, we evolved C. albicans strains that were engineered to mistranslate the CUG codon at constitutively elevated levels, in the presence and absence of the antifungal drug fluconazole. Elevated levels of mistranslation resulted in the rapid acquisition of resistance to fluconazole.
2016-10-27 | E-SYBR-13 | biostudies-arrayexpress
Project description:The structure and composition of the cell walls of different Candida species alone and in response to the antifungal drug, caspofungin, were investigated. The observed differences were used to evaluate how changes at the fungal cell surface affect interactions with macrophages.
2020-05-20 | PXD019293 | Pride
Project description:New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces reporter bioassay in which the yeast heterologously expresses Hik1, a group III hybrid histidine kinase (HHK) from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida, Cryptococcus and molds such as Aspergillus and Rhizopus. Drug-resistant Candida from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against Candida biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, yeast reporter bioassay. Two-color experimental design testing the effects of 2 antifungal compounds (13 and 33) after 0, 20, 40 60 min. In the referred publication, the t=20, 40, 60 data was normalized against the t=0 data
2012-04-30 | E-GEOD-35105 | biostudies-arrayexpress
Project description:The systemic infections by peptogenous fungi member of the genera Candida and Aspergillus represent a serious threat for public health. During previous research we have successfully identified a family of compounds active against different Candida spp. including strains resistant to antifungal drugs currently on the market. We have further refined our knowledge on this field by identifying a possible molecular target that could justify the activity of these compounds. The research of the mode of action of the compounds object of this manuscript was supported also by fluorescent microscopy of labeled derivatives. Transcriptional data indicates that one of the macrocyclic antifungal induces a drug response involving ATP binding cassette transporters. Moreover the data show that the macrocyclic antifungal decrease expression of cell wall biosynthesis genes. Moreover, the quality of the compounds and their potential was tested in vivo revealing a promising profile in particular against fungal infection caused by resistant strains
2015-04-01 | GSE65396 | GEO
Project description:The fungal pathogen Candida albicans and other pathogens of the CTG clade reassigned the leucine CUG codon to serine and tolerate highly variable levels of both serine and leucine at CUG positions in response to environmental cues. Previous studies found that increased leucine misincorporation levels enhance resistance to drugs but the underlying mechanisms are not known. To clarify the biological role of this tuneable codon ambiguity, we evolved C. albicans strains engineered to mistranslate CUG at elevated levels, in the presence and absence of the antifungal drug fluconazole
2017-07-18 | GSE60121 | GEO
Project description:The fungal pathogen Candida albicans and other pathogens of the CTG clade reassigned the leucine CUG codon to serine and tolerate highly variable levels of both serine and leucine at CUG positions in response to environmental cues. Previous studies found that increased leucine misincorporation levels enhance resistance to drugs but the underlying mechanisms are not known. To clarify the biological role of this tuneable codon ambiguity, we evolved C. albicans strains engineered to mistranslate CUG at elevated levels, in the presence and absence of the antifungal drug fluconazole
2017-07-18 | GSE60120 | GEO
Project description:The systemic infections by peptogenous fungi member of the genera Candida and Aspergillus represent a serious threat for public health. During previous research we have successfully identified a family of compounds active against different Candida spp. including strains resistant to antifungal drugs currently on the market. We have further refined our knowledge on this field by identifying a possible molecular target that could justify the activity of these compounds. The research of the mode of action of the compounds object of this manuscript was supported also by fluorescent microscopy of labeled derivatives. Transcriptional data indicates that one of the macrocyclic antifungal induces a drug response involving ATP binding cassette transporters. Moreover the data show that the macrocyclic antifungal decrease expression of cell wall biosynthesis genes. Moreover, the quality of the compounds and their potential was tested in vivo revealing a promising profile in particular against fungal infection caused by resistant strains Gene expression was measured in Candida albians CAF2-1 exposed to the macrocyclic compound FR59 at 3 µM at two time points (15 min and 45 min), The one-color system was used. Three independent experiments were performed using non-exposed cells, 15 min and 45 min exposed cells.
2015-04-01 | E-GEOD-65396 | biostudies-arrayexpress