High impact information on Aureobasidin-A

• Moreover, lag1 Delta lac1 Delta cells are resistant to aureobasidin A, an inhibitor of the inositolphosphorylceramide synthase, suggesting that aureobasidin A may be toxic because it leads to increased ceramide levels [1].
• Aureobasidin A, an inhibitor of the IPC synthase Aur1p completely blocks IPC biosynthesis at 0.5 micrograms/ml but does not block remodeling of glycosylphosphatidylinositol anchors even at concentrations up to 10 micrograms/ml [2].
• Out of seven natural analogues and 18 chemical derivatives of AbA, several were shown to display even more potent Pgp-inhibitory activity [3].
• In contrast, the most potent Pgp inhibitors were found among AbA analogues with [betaHO-MeVal(9)] residue alterations, with some data suggesting a negative impact of the [L-Leu(8)-L-betaHOMeVal(9)-D-Hmp(1)] gamma-turn secondary structure on Pgp inhibitory potential [3].
• Treatment with LY295337, a depsipeptide with antifungal activity, was effective in prolonging survival and reducing fungal counts in brain tissue [4].

Biological context of Aureobasidin-A

• Southern analysis of genomic DNAs of the transformants indicated that the copy number of the plasmid increased from one to more than four, depending on the concentration of AbA used for selection of the transformants [5].
• A single point mutation in the aurA gene of A. nidulans confers a high level of resistance to aureobasidin A [6].
• From a genomic library of one such AUR1 mutant, the AUR1R (for aureobasidin resistant) mutant gene was isolated as a gene that confers resistance to AbA on wild-type cells [7].
• Syntheses of antifungal aureobasidin A analogs with alkyl chains for structure-activity relationship [8].
• In order to investigate possible relationship between the molecular conformation and the amide N-methylation, aureobasidin A (AbA), which exhibits the potent antifungal activity, was subjected to X-ray crystal analysis [9].

Anatomical context of Aureobasidin-A

• Further studies showed that aureobasidin A has effects on macrophages independent of the infecting T. cruzi cells [10].
• The compounds did not interfere with the axenic growth of epimastigotes, but aureobasidin A decreased the release of trypomastigotes from infected murine peritoneal macrophages and the number of intracellular amastigotes in a dose-dependent manner [10].
• We have developed a selection system for hybrids by protoplast fusion using dominant selective drug resistance markers, Tn601(903) against geneticin and AUR1-C against aureobasidin A, and reporter genes, ADH1p-PHO5-ADH1t and CLN2p-CYC1-lacZ, in Saccharomyces cerevisiae [11].

Associations of Aureobasidin-A with other chemical compounds

• The [2,3-dehydro-MeVal(9)]-AbA was the most potent Pgp inhibitory aureobasidin, being 13-fold more potent than AbA and 19-fold more potent (on a molar basis) than CsA [3].
• The resistance to aureobasidin A conferred by the MDR2/Pgp as well as by the MDR1/Pgp was overcome by vinblastine, verapamil, and cyclosporin A, depending on their concentrations, but not by colchicine [12].
• The 2mu-based pCRE3 carries the aureobasidin A, zeocin and URA3 markers. pCRE3 proved to be easily cured without active counter-selection [13].
• The minimum inhibitory concentration (MIC) was determined by the broth microdilution method for LY295337 in SDB and RPMI 1640, and for fluconazole by an agar dilution method [14].

Gene context of Aureobasidin-A

• Mutations in AUR1 had been shown previously to give resistance to the antifungal drug aureobasidin A, leading us to predict that the drug should inhibit IPC synthase activity [15].
• A N- and C-terminally truncated portion of the mutant FAS2 gene was subcloned to an integrating plasmid containing an aureobasidin A-resistant transformation marker and a galactose-inducible growth inhibitory sequence (GAL10p::GIN11) [16].

References