scholarly journals A p53-like transcription factor similar to Ndt80 controls the response to nutrient stress in the filamentous fungus, Aspergillus nidulans

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 72 ◽  
Author(s):  
Margaret E Katz ◽  
Kathryn Braunberger ◽  
Gauncai Yi ◽  
Sarah Cooper ◽  
Heather M Nonhebel ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Transcriptional Profiling ◽  
Nutrient Stress ◽  
Nutrient Sensing ◽  
Carbon Limitation ◽  
Nutrient Depletion ◽  
Null Mutant ◽  
Global Regulator ◽  
Extracellular Proteases ◽  
Number Of Genes

TheAspergillus nidulans xprGgene encodes a putative transcriptional activator that is a member of the Ndt80 family in the p53-like superfamily of proteins. Previous studies have shown that XprG controls the production of extracellular proteases in response to starvation. We undertook transcriptional profiling to investigate whether XprG has a wider role as a global regulator of the carbon nutrient stress response. Our microarray data showed that the expression of a large number of genes, including genes involved in secondary metabolism, development, high-affinity glucose uptake and autolysis, were altered in anxprGΔnull mutant. Many of these genes are known to be regulated in response to carbon starvation. We confirmed that sterigmatocystin and penicillin production is reduced inxprG-mutants. The loss of fungal mass and secretion of pigments that accompanies fungal autolysis in response to nutrient depletion was accelerated in anxprG1gain-of-function mutant and decreased or absent in anxprG-mutant. The results support the hypothesis that XprG plays a major role in the response to carbon limitation and that nutrient sensing may represent one of the ancestral roles for the p53-like superfamily. Disruption of the AN6015 gene, which encodes a second Ndt80-like protein, showed that it is required for sexual reproduction inA. nidulans.

scholarly journals The Aspergillus nidulans xprF Gene Encodes a Hexokinase-like Protein Involved in the Regulation of Extracellular Proteases

Genetics ◽  
2000 ◽  
Vol 156 (4) ◽  
pp. 1559-1571 ◽  
Author(s):  
Margaret E Katz ◽  
Amir Masoumi ◽  
Stephen R Burrows ◽  
Carolyn G Shirtliff ◽  
Brian F Cheetham
Keyword(s):  
Sequence Analysis ◽  
Aspergillus Nidulans ◽  
Carbon Limitation ◽  
Extracellular Proteases ◽  
Nonsense Mutations ◽  
Acid Protein ◽  
Catalytic Role ◽  
New Type ◽  
Protease Deficient ◽  
A Minor

Abstract The extracellular proteases of Aspergillus nidulans are produced in response to limitation of carbon, nitrogen, or sulfur, even in the absence of exogenous protein. Mutations in the A. nidulans xprF and xprG genes have been shown to result in elevated levels of extracellular protease in response to carbon limitation. The xprF gene was isolated and sequence analysis indicates that it encodes a 615-amino-acid protein, which represents a new type of fungal hexokinase or hexokinase-like protein. In addition to their catalytic role, hexokinases are thought to be involved in triggering carbon catabolite repression. Sequence analysis of the xprF1 and xprF2 alleles showed that both alleles contain nonsense mutations. No loss of glucose or fructose phosphorylating activity was detected in xprF1 or xprF2 mutants. There are two possible explanations for this observation: (1) the xprF gene may encode a minor hexokinase or (2) the xprF gene may encode a protein with no hexose phosphorylating activity. Genetic evidence suggests that the xprF and xprG genes are involved in the same regulatory pathway. Support for this hypothesis was provided by the identification of a new class of xprG- mutation that suppresses the xprF1 mutation and results in a protease-deficient phenotype.

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

scholarly journals CodY Is a Global Regulator of Virulence-Associated Properties for Clostridium perfringens Type D Strain CN3718

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Jihong Li ◽  
Menglin Ma ◽  
Mahfuzur R. Sarker ◽  
Bruce A. McClane
Keyword(s):  
Clostridium Perfringens ◽  
Null Mutant ◽  
Intestinal Infection ◽  
Wild Type ◽  
Global Regulator ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Type D ◽  
Epsilon Toxin ◽  
Virulence Properties

ABSTRACT CodY is known to regulate various virulence properties in several Gram-positive bacteria but has not yet been studied in the important histotoxic and intestinal pathogen Clostridium perfringens. The present study prepared an isogenic codY-null mutant in C. perfringens type D strain CN3718 by insertional mutagenesis using the Targetron system. Western blot analysis indicated that, relative to wild-type CN3718 or a complementing strain, this isogenic codY mutant produces reduced levels of epsilon toxin (ETX). Using supernatants from cultures of the wild-type, codY-null mutant, and complementing strains, CodY regulation of ETX production was shown to have cytotoxic consequences for MDCK cells. The CodY regulatory effect on ETX production was specific, since the codY-null mutant still made wild-type levels of alpha-toxin and perfringolysin O. Sialidase activity measurements and sialidase Western blot analysis of supernatants from CN3718 and its isogenic derivatives showed that CodY represses overall exosialidase activity due to a reduced presence of NanH in culture supernatants. Inactivation of the codY gene significantly decreased the adherence of CN3718 vegetative cells or spores to host Caco-2 cells. Finally, the codY mutant showed increased spore formation under vegetative growth conditions, although germination of these spores was impaired. Overall, these results identify CodY as a global regulator of many C. perfringens virulence-associated properties. Furthermore, they establish that, via CodY, CN3718 coordinately regulates many virulence-associated properties likely needed for intestinal infection. IMPORTANCE Clostridium perfringens is a major human and livestock pathogen because it produces many potent toxins. C. perfringens type D strains cause intestinal infections by producing toxins, especially epsilon toxin (ETX). Previous studies identified CodY as a regulator of certain virulence properties in other Gram-positive bacteria. Our study now demonstrates that CodY is a global regulator of virulence-associated properties for type D strain CN3718. It promotes production of ETX, attachment of CN3718 vegetative cells or spores to host enterocyte-like Caco-2 cells, and spore germination; the last two effects may assist intestinal colonization. In contrast, CodY represses sporulation. These results provide the first evidence that CodY can function as a global regulator of C. perfringens virulence-associated properties and that this strain coordinately regulates its virulence-associated properties using CodY to increase ETX production, host cell attachment, and spore germination but to repress sporulation, as would be optimal during type D intestinal infection.

scholarly journals A Dihydroflavonoid Naringin Extends the Lifespan of C. elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Qing Zhu ◽  
Yuan Qu ◽  
Xiao-Gang Zhou ◽  
Jian-Ning Chen ◽  
Huai-Rong Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Biological Activities ◽  
Nutrient Sensing ◽  
Null Mutant ◽  
Oxidative Stress Tolerance ◽  
C Elegans ◽  
Expression Of Genes ◽  
Wide Range ◽  
And Oxidative Stress

Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of Caenorhabditis elegans (C. elegans). Our results showed that naringin could extend the lifespan of C. elegans. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in C. elegans models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as daf-2, akt-2, akt-1, eat-2, sir-2.1, and rsks-1. Naringin treatment prolonged the lifespan of long-lived glp-1 mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by daf-16 and itself. In conclusion, we show that a natural product naringin could extend the lifespan of C. elegans and delay the progression of aging-related diseases in C. elegans models via DAF-16.

scholarly journals Transcriptome Analysis of NF-κB- and Phosphatidylinositol 3-Kinase-Regulated Genes in Human Cytomegalovirus-Infected Monocytes

2007 ◽  
Vol 82 (2) ◽  
pp. 1040-1046 ◽  
Author(s):  
Gary Chan ◽  
Elizabeth R. Bivins-Smith ◽  
M. Shane Smith ◽  
Andrew D. Yurochko
Keyword(s):  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Transcriptional Profiling ◽  
Dependent Manner ◽  
Control Points ◽  
Phosphatidylinositol 3 Kinase ◽  
Number Of Genes ◽  
Cellular Control ◽  
Rapid Activation ◽  
Phosphatidylinositol 3

ABSTRACT Human cytomegalovirus induces a proinflammatory monocyte following infection, and we have evidence that NF-κB and phosphatidylinositol 3-kinase [PI(3)K] are key mediators in this early activation. To begin to address how these signaling pathways are responsible for the rapid activation of infected monocytes, we examined the role that these pathways played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed that a significant number of genes, including inflammatory genes, were regulated in an NF-κB- and/or PI(3)K-dependent manner, identifying the NF-κB and PI(3)K pathways as key cellular control points in the conversion of monocytes to an activated proinflammatory state following HCMV infection.

scholarly journals TetR-Type Transcriptional Regulator VtpR Functions as a Global Regulator in Vibrio tubiashii

2009 ◽  
Vol 75 (24) ◽  
pp. 7602-7609 ◽  
Author(s):  
Hiroaki Hasegawa ◽  
Claudia C. Häse
Keyword(s):  
Virulence Factors ◽  
Elevated Temperatures ◽  
Extracellular Proteins ◽  
Protease Production ◽  
High Homology ◽  
Global Regulator ◽  
Extracellular Proteases ◽  
Negative Effects ◽  
Vibrio Tubiashii ◽  
Protein Functions

ABSTRACT Vibrio tubiashii, a causative agent of severe shellfish larval disease, produces multiple extracellular proteins, including a metalloprotease (VtpA), as potential virulence factors. We previously reported that VtpA is toxic for Pacific oyster (Crassostrea gigas) larvae. In this study, we show that extracellular protease production by V. tubiashii was much reduced by elevated salt concentrations, as well as by elevated temperatures. In addition, V. tubiashii produced dramatically less protease in minimal salts medium supplemented with glucose or sucrose as the sole carbon source than with succinate. We identified a protein that belongs to the TetR family of transcriptional regulators, VtpR, which showed high homology with V. cholerae HapR. We conclude that VtpR activates VtpA production based on the following: (i) a VtpR-deficient V. tubiashii mutant did not produce extracellular proteases, (ii) the mutant showed reduced expression of a vtpA-lacZ fusion, and (iii) VtpR activated vtpA-lacZ in a V. cholerae heterologous background. Moreover, we show that VtpR activated the expression of an additional metalloprotease gene (vtpB). The deduced VtpB sequence showed high homology with a metalloprotease, VhpA, from V. harveyi. Furthermore, the vtpR mutant strain produced reduced levels of extracellular hemolysin, which is attributed to the lower expression of the V. tubiashii hemolysin genes (vthAB). The VtpR-deficient mutant also had negative effects on bacterial motility and did not demonstrate toxicity to oyster larvae. Together, these findings establish that the V. tubiashii VtpR protein functions as a global regulator controlling an array of potential virulence factors.

Analysis of Two Aspergillus nidulans Genes Encoding Extracellular Proteases

2000 ◽  
Vol 29 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Patricia A vanKuyk ◽  
Brian F Cheetham ◽  
Margaret E Katz
Keyword(s):  
Aspergillus Nidulans ◽  
Extracellular Proteases ◽  
Genes Encoding

scholarly journals Transcriptional Profiling of Target of RNAIII-Activating Protein, a Master Regulator of Staphylococcal Virulence

2005 ◽  
Vol 73 (10) ◽  
pp. 6220-6228 ◽  
Author(s):  
Moshe Korem ◽  
Yael Gov ◽  
Madanahally D. Kiran ◽  
Naomi Balaban
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Transcriptional Profiling ◽  
Protein A ◽  
Cell Communication ◽  
Global Regulator ◽  
Positive Bacterium ◽  
Master Regulator ◽  
Expression Of Genes ◽  
Histidine Phosphorylation

ABSTRACT Staphylococcus aureus is a gram-positive bacterium that is part of the normal healthy flora but that can become virulent and cause infections by producing biofilms and toxins. The production of virulence factors is regulated by cell-cell communication (quorum sensing) through the histidine phosphorylation of target of RNAIII-activating protein (TRAP), which is a 21-kDa protein that is highly conserved among staphylococci. Using microarray analysis, we show here that the expression and phosphorylation of TRAP upregulate the expression of most, if not all, toxins known to date, as well as their global regulator agr. In addition, we show here that the expression and phosphorylation of TRAP are also necessary for the expression of genes known to be necessary for the survival of the bacteria in a biofilm, like arc, pyr, and ure. TRAP is thus demonstrated to be a master regulator of staphylococcal pathogenesis.

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