scholarly journals Role of the PDR Gene Network in Yeast Susceptibility to the Antifungal Antibiotic Mucidin

2000 ◽  
Vol 44 (2) ◽  
pp. 418-420 ◽  
Author(s):  
Dana Michalkova-Papajova ◽  
Margita Obernauerova ◽  
Julius Subik
Keyword(s):  
Transcriptional Regulation ◽  
Gene Network ◽  
Wild Type ◽  
Gain Of Function ◽  
Antifungal Antibiotic ◽  
Yeast Strains ◽  
Yeast Mutants ◽  
Type Strains ◽  
Higher Sensitivity

ABSTRACT Yeast strains disrupted in the PDR1, PDR3, or PDR5 gene, but not in SNQ2, exhibited higher sensitivity to mucidin (strobilurin A) than did the isogenic wild-type strains. Different gain-of-function mutations in the PDR1and PDR3 genes rendered yeast mutants resistant to this antibiotic. Mucidin induced PDR5 expression, but the changes in the expression of SNQ2 were only barely detectable. The results indicate that PDR5 provides the link between transcriptional regulation by PDR1 andPDR3 and mucidin resistance of yeast.

Characterization of the Role of the FluG Protein in Asexual Development of Aspergillus nidulans

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1027-1036 ◽  
Author(s):  
Cletus A D'Souza ◽  
Bee Na Lee ◽  
Thomas H Adams
Keyword(s):  
Aspergillus Nidulans ◽  
Negative Influence ◽  
Asexual Development ◽  
Wild Type ◽  
Significant Similarity ◽  
Developmental Defects ◽  
Asexual Sporulation ◽  
Type Strains

Abstract We showed previously that a ΔfluG mutation results in a block in Aspergillus nidulans asexual sporulation and that overexpression of fluG activates sporulation in liquid-submerged culture, a condition that does not normally support sporulation of wild-type strains. Here we demonstrate that the entire N-terminal region of FluG (∼400 amino acids) can be deleted without affecting sporulation, indicating that FluG activity resides in the C-terminal half of the protein, which bears significant similarity with GSI-type glutamine synthetases. While FluG has no apparent role in glutamine biosynthesis, we propose that it has an enzymatic role in sporulation factor production. We also describe the isolation of dominant suppressors of ΔfluG(dsg) that should identify components acting downstream of FluG and thereby define the function of FluG in sporulation. The dsgA1 mutation also suppresses the developmental defects resulting from ΔflbA and dominant activating fadA mutations, which both cause constitutive induction of the mycelial proliferation pathway. However, dsgA1 does not suppress the negative influence of these mutations on production of the aflatoxin precursor, sterigmatocystin, indicating that dsgA1 is specific for asexual development. Taken together, our studies define dsgA as a novel component of the asexual sporulation pathway.

scholarly journals Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9015
Author(s):  
Daniel Janitschke ◽  
Anna A. Lauer ◽  
Cornel M. Bachmann ◽  
Martin Seyfried ◽  
Heike S. Grimm ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Expression Patterns ◽  
Wild Type ◽  
Neuronal Function ◽  
Purine Base ◽  
Unique Role ◽  
Beneficial Effects ◽  
Other Substances

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.

scholarly journals Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nilay Nandi ◽  
Lauren K Tyra ◽  
Drew Stenesen ◽  
Helmut Krämer
Keyword(s):  
Drosophila Melanogaster ◽  
Nuclear Protein ◽  
Protective Role ◽  
Alpha Synuclein ◽  
Wild Type ◽  
Gain Of Function ◽  
Mitotic Kinase

Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized AcnS437D. Expression of aggregation-prone polyQ-containing proteins or the Amyloid-β42 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges.

scholarly journals The Role of Ethylene Production in Virulence of Pseudomonas syringae pvs. glycinea and phaseolicola

2001 ◽  
Vol 91 (5) ◽  
pp. 511-518 ◽  
Author(s):  
Helge Weingart ◽  
Henriette Ullrich ◽  
Klaus Geider ◽  
Beate Völksch
Keyword(s):  
Pseudomonas Syringae ◽  
Ethylene Production ◽  
Type Strain ◽  
Wild Type Strain ◽  
Wild Type ◽  
In Planta ◽  
Population Sizes ◽  
Soybean Plants ◽  
Type Strains

The importance of ethylene production for virulence of Pseudomonas syringae pvs. glycinea and phaseolicola was assayed by comparing bacterial multiplication and symptom development in bean and soybean plants inoculated with ethylene-negative (efe) mutants and wild-type strains. The efe mutants of Pseudomonas syringae pv. glycinea were significantly reduced in their ability to grow in planta. However, the degree of reduction was strain-dependent. Population sizes of efe mutant 16/83-E1 that did not produce the phototoxin coronatine were 10- and 15-fold lower than those of the wild-type strain on soybean and on bean, and 16/83-E1 produced very weak symptoms compared with the wild-type strain. The coronatine-producing efe mutant 7a/90-E1 reached fourfold and twofold lower population sizes compared with the wild-type strain on soybean and bean, respectively, and caused disease symptoms typical of the wild-type strain. Experiments with ethylene-insensitive soybeans confirmed these results. The virulence of the wild-type strains was reduced to the same extent in ethylene-insensitive soybean plants as the virulence of the efe mutants in ethylene-susceptible soybeans. In contrast, the virulence of Pseudomonas syringae pv. phaseolicola was not affected by disruption of the efe gene.

scholarly journals New Insights into the Potential Cytotoxic Role of Bacillus cytotoxicus Cytotoxin K-1

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 698
Author(s):  
Klèma Marcel Koné ◽  
Pauline Hinnekens ◽  
Jelena Jovanovic ◽  
Andreja Rajkovic ◽  
Jacques Mahillon
Keyword(s):  
Bacillus Cereus ◽  
Tetrazolium Salt ◽  
Wild Type ◽  
Foodborne Outbreak ◽  
Pathogenic Role ◽  
Bacillus Cereus Group ◽  
Mtt Method ◽  
High Cytotoxicity ◽  
Type Strains

The thermotolerant representative of the Bacillus cereus group, Bacillus cytotoxicus, reliably harbors the coding gene of cytotoxin K-1 (CytK-1). This protein is a highly cytotoxic variant of CytK toxin, initially recovered from a diarrheal foodborne outbreak that caused the death of three people. In recent years, the cytotoxicity of B. cytotoxicus has become controversial, with some strains displaying a high cytotoxicity while others show no cytotoxicity towards cell lines. In order to better circumscribe the potential pathogenic role of CytK-1, knockout (KO) mutants were constructed in two B. cytotoxicus strains, E8.1 and E28.3. The complementation of the cytK-1 KO mutation was implemented in a mutant strain lacking in the cytK-1 gene. Using the tetrazolium salt (MTT) method, cytotoxicity tests of the cytK-1 KO and complemented mutants, as well as those of their wild-type strains, were carried out on Caco-2 cells. The results showed that cytK-1 KO mutants were significantly less cytotoxic than the parental wild-type strains. However, the complemented mutant was as cytotoxic as the wild-type, suggesting that CytK-1 is the major cytotoxicity factor in B. cytotoxicus.

scholarly journals Genetic-metabolic coupling for targeted metabolic engineering

2017 ◽  
Author(s):  
Stefano Cardinale ◽  
Felipe Gonzalo Tueros ◽  
Morten Otto Alexander Sommer
Keyword(s):  
Gene Network ◽  
Production Optimization ◽  
Wild Type ◽  
Chemical Production ◽  
Iron Storage ◽  
Metabolic Coupling ◽  
Transposon Mutants ◽  
Thiamine Biosynthesis ◽  
Type Strains ◽  
Coupling Cell

SUMMARYTo produce chemicals, microbes typically employ potent biosynthetic enzymes that interact with native metabolism to affect cell fitness as well as chemical production. However, production optimization largely relies on data collected from wild type strains in the absence of metabolic perturbations, thus limiting their relevance to specific process scenarios. Here, we address this issue by coupling cell fitness to the production of thiamine diphosphate in Escherichia coli using a synthetic RNA biosensor.We apply this system to interrogate a library of transposon mutants to elucidate the native gene network influencing both cell fitness and thiamine production. Specifically, we identify uncharacterized effectors of the OxyR-SoxR stress response that limit thiamine biosynthesis via alternative regulation of iron storage and Fe-S-cluster inclusion in enzymes.Our study represents a new generalizable approach for the reliable high-throughput identification of genetic targets of both known and unknown function that are directly relevant to a specific biosynthetic process.

scholarly journals Doubling Ty1 element copy number in Saccharomyces cerevisiae: host genome stability and phenotypic effects.

Genetics ◽  
1991 ◽  
Vol 129 (4) ◽  
pp. 1043-1052
Author(s):  
J D Boeke ◽  
D J Eichinger ◽  
G Natsoulis
Keyword(s):  
Copy Number ◽  
Genome Stability ◽  
Genome Structure ◽  
Yeast Cells ◽  
Wild Type ◽  
Opposite Mating Type ◽  
Spore Viability ◽  
Normal Number ◽  
Yeast Strains ◽  
Type Strains

Abstract Haploid yeast strains bearing approximately double the normal number of Ty1 elements have been constructed using marked GAL/Ty1 fusion plasmids. The strains maintain their high transposon copy number and overall genome structure in the absence of selection. The strains bearing extra Ty1 copies are surprisingly similar phenotypically to the parental strain. The results suggest that the limit to transposon copy number, if any, has not been reached. When these strains are crossed by wild-type strains (i.e., bearing the normal complement of Ty1 elements) or by strains of opposite mating type also bearing excess Ty1 elements, normal to very slightly reduced spore viability is observed, indicating that increasing the extent of transposon homology scattered around the genome does not result in significant increases in frequency of ectopic reciprocal recombination. The results suggest that yeast cells have evolved mechanisms for coping with excess transposon copies in the genome.

scholarly journals MUTATIONS IN THE PHO80 GENE CONFER PERMEABILITY TO 5'-MONONUCLEOTIDES IN SACCHAROMYCES CEREVISIAE

Genetics ◽  
1982 ◽  
Vol 102 (3) ◽  
pp. 341-359
Author(s):  
Linda F Bisson ◽  
Jeremy Thorner
Keyword(s):  
Inorganic Phosphate ◽  
Phosphate Transport ◽  
Culture Conditions ◽  
Yeast Cells ◽  
Wild Type ◽  
Coordinate Control ◽  
Complementation Groups ◽  
The Right ◽  
Yeast Mutants ◽  
Type Strains

ABSTRACT Yeast mutants permeable to dTMP (tup) were selected and two new complementation groups (tup5 and tup7) were identified. Assay of the levels of both acid and alkaline phosphatase in cells grown under either repressing (5 mm PO4  -3) or derepressing (0.03 mm PO4  -3) conditions indicated that, in general, tup mutations cause cells to be defective in their regulation of phosphatase synthesis. In addition, three of the tup mutations (tup1, tup4 and tup7) displayed markedly elevated rates of inorganic phosphate transport. The tup7 locus was found to be tightly centromere-linked on the right arm of chromosome XV, and was shown to be allelic with the pho80 regulatory locus on the basis of both genetic and biochemical criteria. Analysis of other mutations known to affect phosphatase levels (pho) indicated that some also conferred permeability to dTMP. Possible allelic relationships between tup genes and certain of these pho mutations are discussed. Regardless of the culture conditions, wild-type strains were not permeable to dTMP; in contrast, it was found in the course of this work that normal yeast cells were permeable to dUMP and that dUMP permeability was regulated by the concentration of inorganic phosphate present in the medium used to grow the cells. Thus, permeability to 5′-mononucleotides appears to be under coordinate control with phosphatase synthesis.

RNA processing and expression of an intron-encoded protein in yeast mitochondria: role of a conserved dodecamer sequence

1987 ◽  
Vol 7 (7) ◽  
pp. 2530-2537 ◽  
Author(s):  
H Zhu ◽  
I G Macreadie ◽  
R A Butow
Keyword(s):  
Rna Processing ◽  
Rrna Gene ◽  
Yeast Mitochondria ◽  
Wild Type ◽  
Reading Frame ◽  
Processing Activity ◽  
Novel Processing ◽  
Type Strains ◽  
Upstream Exon

The 3' ends of most Saccharomyces cerevisiae mitochondrial mRNAs terminate at a conserved dodecamer sequence, 5'-AAUAAUAUUCUU-3', of unknown function. We have studied the consequences of mutations within a dodecamer found in an 1,143-base-pair optional intron of the mitochondrial large (21S) rRNA gene on RNA processing. The dodecamer is situated at the 3' end of an expressed open reading frame (ORF) within that intron, and the mutations are two adjacent transversions that extend the intron ORF by 51 nucleotides. The strain harboring these mutations, L5-10-1, is defective in biased intron transmission in crosses to strains that lack the intron, as are other mutants which contain nucleotide changes within the ORF (I. G. Macreadie, R. M. Scott, A. R. Zinn, and R. A. Butow, Cell 41:395-402, 1985). However, unlike these other mutants, wild-type strains, or petites which retain the intron allele, L5-10-1 is defective in processing at the intron dodecamer. In addition, L5-10-1 lacks a prominent 2.7-kilobase RNA containing both intron and exon sequences and at least two of four RNAs that correspond to various forms of the excised intron. We propose that these RNAs, missing in L5-10-1 but present in all other strains examined, arise in part by processing at the intron dodecamer. In addition, in all strains examined, we have detected a novel processing activity in which precursor 21S rRNA transcripts are cleaved in the upstream exon, about 1,500 nucleotides from the 5' end of the RNA. This activity, together with 3' intron dodecamer cleavage, probably accounts for the 2.7-kilobase RNA species, a candidate for the mRNA for the intron-encoded protein.

scholarly journals Allele Substitution of the Streptokinase Gene Reduces the Nephritogenic Capacity of Group A Streptococcal Strain NZ131

2000 ◽  
Vol 68 (3) ◽  
pp. 1019-1025 ◽  
Author(s):  
Annika Nordstrand ◽  
W. Michael McShan ◽  
Joseph J. Ferretti ◽  
Stig E. Holm ◽  
Mari Norgren
Keyword(s):  
Allelic Variant ◽  
Wild Type ◽  
Poststreptococcal Glomerulonephritis ◽  
Acute Poststreptococcal Glomerulonephritis ◽  
Site Specific Integration ◽  
Allele Substitution ◽  
Group A ◽  
Type Strains ◽  
Streptococcal Strain

ABSTRACT To investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strainStreptococcus equisimilis H46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131. The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN. The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain. The mutant and the wild-type strains produced equivalent amounts of streptokinase. Complementation of the ska deletion derivative with the original ska allele reconstituted the nephritogenicity of wild-type NZ131. The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.

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