Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification and characterization of potent, broad-spectrum antifungal compounds using a yeast reporter bioassay.

ABSTRACT: 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

ORGANISM(S): Candida albicans

SUBMITTER: Andre Nantel

PROVIDER: E-GEOD-35105 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Identification and characterization of potent, broad-spectrum antifungal compounds using a yeast reporter bioassay.

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.

2012-05-01 | GSE35105 | GEO

In depth characterization of the activity of a novel synthetic macrocyclic antifungal compound

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

Inhibition of Pseudomonas aeruginosa swarming motility by 1-naphthol and other bicyclic compounds bearing hydroxyl group.

Project description:Many bacteria convert bicyclic compounds, such as indole and naphthalene, to oxidized compounds, including hydroxyindoles and naphthols. Pseudomonas aeruginosa, a ubiquitous bacterium that inhabits diverse environments, shows pathogenicity against animals, plants and other microorganisms, and increasing evidence has shown that several bicyclic compounds alter the virulence-related phenotypes of P. aeruginosa. Here, we revealed that hydroxyindoles (4- and 5-hydroxyindoles) and naphthalene derivatives bearing hydroxyl groups specifically inhibit swarming motility but have minor effects on other motilities, including swimming and twitching, in P. aeruginosa. Further analyses using 1-naphthol showed that this effect is also associated with clinically isolated hyper swarming P. aeruginosa cells. Swarming motility is associated with the dispersion of cells from biofilms, and the addition of 1-naphthol maintained biofilm biomass without cell dispersion. Swarming inhibition did not mediate rhamnolipid production, which regulates swarming motility in P. aeruginosa. Transcriptome analyses revealed that 1-naphthol increases gene expression associated with multidrug efflux and represses gene expression associated with aerotaxis and pyochelin, flagellar, and pili synthesis. In the present study, we showed that several bicyclic compounds bearing hydroxyl groups inhibit the swarming motility of P. aeruginosa, and these results provide new insight into the chemical structures that inhibit the specific phenotypes of P. aeruginosa. In total 4 samples: gene expressions of P. aeruginosa with (2 samples) or without (2 samples) 1-naphthol

2015-02-20 | E-GEOD-60343 | biostudies-arrayexpress

In depth characterization of the activity of a novel synthetic macrocyclic antifungal compound

2015-04-01 | E-GEOD-65396 | biostudies-arrayexpress

Cooperative function of the three different kinds of nucleoid-associated proteins encoded on the IncP-7 plasmid pCAR1 [KT2440 chromosome chip]

Project description:Nucleoid-associated proteins (NAPs) are known to fold bacterial DNA and influence global transcription. Incompatibility P-7 plasmid pCAR1 carries three genes encoding NAPs: H-NS family protein Pmr, NdpA-like protein Pnd, and HU-like protein Phu. Because previous reports about plasmid-encoded NAPs mainly focused on H-NS homologs, functions and importance of different kinds of NAPs encoded on a plasmid remained unknown. Here, we assessed the effects of single or double disruption of pmr, pnd, and phu in a host P. putida KT2440. When pmr and pnd or pmr and phu were disrupted simultaneously, stability and conjugation frequency of pCAR1 decreased significantly. In the comprehensive phenotypes comparisons, host availabilities of some compounds, which were reduced by pCAR1carriage, were restored by NAP-gene(s)-disruption. Transcriptome analyses showed that Pmr and Pnd have different regulons, whereas Phu mainly supports their gene regulation. These cooperative functions of the three NAPs were not simply due to protein-protein interactions because hetero-oligomers of them were not detected in pull-down assays. Our present study is the first report about the cooperative function of plasmid-encoded different kinds of NAPs, which show no homology with each other. The NAPs-dependent change of chromosomal RNA maps in early exponential phases.

2013-12-07 | E-GEOD-53067 | biostudies-arrayexpress

Cooperative function of the three different kinds of nucleoid-associated proteins encoded on the IncP-7 plasmid pCAR1 [pCAR1 plasmid chip]

2013-12-07 | E-GEOD-53068 | biostudies-arrayexpress

Gene profile of mid-log phase of SD medium grown Candida albicans rhb1 gene deletion strain

Project description:Candida albicans is an opportunistic pathogenic yeast that is commensally found in variety of host niches. Rhb1 serves as an positive regulator of Tor1 kinase which is the central component of the TOR signaling in controlling several virulence factors. Here, we used microarray to determined changes in transcript profile while the cell lacks the RHB1 gene. 10 array generated by six batchs of individual experiment (from cell isolation to culture); each included one flask of wild type culture (SC5314) and one flask of rhb1M-bM-^HM-^F (CCT-D1)mutant culture.

2012-03-15 | E-GEOD-29128 | biostudies-arrayexpress

Miguel Teixeira

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

2015-07-06 | MSV000079183 | MassIVE

Miguel Teixeira (Modified)

2015-08-04 | MSV000079209 | MassIVE