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Braz. j. med. biol. res ; 49(7): e5313, 2016. tab, graf
Article in English | LILACS | ID: biblio-951690


Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees.

Animals , Ascomycota/drug effects , Bees/microbiology , Lignans/pharmacology , Mitogen-Activated Protein Kinases/drug effects , Saccharomyces cerevisiae Proteins/drug effects , Antifungal Agents/pharmacology , Tetrazolium Salts , Time Factors , Microbial Sensitivity Tests , Blotting, Western , Mitogen-Activated Protein Kinases/analysis , Saccharomyces cerevisiae Proteins/analysis , Drug Synergism , Formazans , Larva/drug effects , Larva/microbiology , Larva/pathogenicity , Mycoses/drug therapy
Genet. mol. res. (Online) ; 1(1): 79-89, Mar. 2002.
Article in English | LILACS | ID: lil-417649


The sensitivity responses of seven pso mutants of Saccharomyces cerevisiae towards the mutagens N-nitrosodiethylamine (NDEA), 1,2:7,8-diepoxyoctane (DEO), and 8-hydroxyquinoline (8HQ) further substantiated their allocation into two distinct groups: genes PSO1 (allelic to REV3), PSO2 (SNM1), PSO4 (PRP19), and PSO5 (RAD16) constitute one group in that they are involved in repair of damaged DNA or in RNA processing whereas genes PSO6 (ERG3) and PSO7 (COX11) are related to metabolic steps protecting from oxidative stress and thus form a second group, not responsible for DNA repair. PSO3 has not yet been molecularly characterized but its pleiotropic phenotype would allow its integration into either group. The first three PSO genes of the DNA repair group and PSO3, apart from being sensitive to photo-activated psoralens, have another common phenotype: they are also involved in error-prone DNA repair. While all mutants of the DNA repair group and pso3 were sensitive to DEO and NDEA the pso6 mutant revealed WT or near WT resistance to these mutagens. As expected, the repair-proficient pso7-1 and cox11-Delta mutant alleles conferred high sensitivity to NDEA, a chemical known to be metabolized via redox cycling that yields hydroxylamine radicals and reactive oxygen species. All pso mutants exhibited some sensitivity to 8HQ and again pso7-1 and cox11-Delta conferred the highest sensitivity to this drug. Double mutant snm1-Delta cox11-Delta exhibited additivity of 8HQ and NDEA sensitivities of the single mutants, indicating that two different repair/recovery systems are involved in survival. DEO sensitivity of the double mutant was equal or less than that of the single snm1-Delta mutant. In order to determine if there was oxidative damage to nucleotide bases by these drugs we employed an established bacterial test with and without metabolic activation. After S9-mix biotransformation, NDEA and to a lesser extent 8HQ, lead to significantly higher mutagenesis in an Escherichia coli tester strain WP2-IC203 as compared to WP2, whereas DEO-induced mutagenicity remained unchanged

DNA, Fungal/genetics , Oxidative Stress/genetics , Mutagens/toxicity , DNA Repair/genetics , Saccharomyces cerevisiae/genetics , Epoxy Compounds/toxicity , DNA, Fungal/drug effects , DNA Damage/drug effects , DNA Damage/genetics , Diethylnitrosamine/toxicity , Genes, Fungal , Oxyquinoline/toxicity , Phenotype , Saccharomyces cerevisiae Proteins/drug effects , Saccharomyces cerevisiae Proteins/genetics , DNA Repair/drug effects , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/drug effects