scholarly journals Glucose-Dependent Activation of Bacillus anthracis Toxin Gene Expression and Virulence Requires the Carbon Catabolite Protein CcpA

2010 ◽  
Vol 193 (1) ◽  
pp. 52-62 ◽  
Author(s):  
C. Chiang ◽  
C. Bongiorni ◽  
M. Perego
Keyword(s):  
Gene Expression ◽  
Bacillus Anthracis ◽  
Toxin Gene ◽  
Toxin Gene Expression

scholarly journals The Global Regulator CodY Regulates Toxin Gene Expression in Bacillus anthracis and Is Required for Full Virulence

2009 ◽  
Vol 77 (10) ◽  
pp. 4437-4445 ◽  
Author(s):  
Willem van Schaik ◽  
Alice Château ◽  
Marie-Agnès Dillies ◽  
Jean-Yves Coppée ◽  
Abraham L. Sonenshein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Anthracis ◽  
Mutant Strain ◽  
Virulence Gene ◽  
Etiologic Agent ◽  
Toxin Gene ◽  
Promoter Regions ◽  
Virulence Gene Expression ◽  
Toxin Gene Expression ◽  
Virulence Regulator

ABSTRACT In gram-positive bacteria, CodY is an important regulator of genes whose expression changes upon nutrient limitation and acts as a repressor of virulence gene expression in some pathogenic species. Here, we report the role of CodY in Bacillus anthracis, the etiologic agent of anthrax. Disruption of codY completely abolished virulence in a toxinogenic, noncapsulated strain, indicating that the activity of CodY is required for full virulence of B. anthracis. Global transcriptome analysis of a codY mutant and the parental strain revealed extensive differences. These differences could reflect direct control for some genes, as suggested by the presence of CodY binding sequences in their promoter regions, or indirect effects via the CodY-dependent control of other regulatory proteins or metabolic rearrangements in the codY mutant strain. The differences included reduced expression of the anthrax toxin genes in the mutant strain, which was confirmed by lacZ reporter fusions and immunoblotting. The accumulation of the global virulence regulator AtxA protein was strongly reduced in the mutant strain. However, in agreement with the microarray data, expression of atxA, as measured using an atxA-lacZ transcriptional fusion and by assaying atxA mRNA, was not significantly affected in the codY mutant. An atxA-lacZ translational fusion was also unaffected. Overexpression of atxA restored toxin component synthesis in the codY mutant strain. These results suggest that CodY controls toxin gene expression by regulating AtxA accumulation posttranslationally.

scholarly journals The Alternative Sigma Factor σH Is Required for Toxin Gene Expression by Bacillus anthracis

2006 ◽  
Vol 189 (5) ◽  
pp. 1874-1883 ◽  
Author(s):  
Maria Hadjifrangiskou ◽  
Yahua Chen ◽  
Theresa M. Koehler
Keyword(s):  
Gene Expression ◽  
Bacillus Anthracis ◽  
Sigma Factor ◽  
State Level ◽  
Growth Conditions ◽  
Exponential Phase ◽  
Toxin Gene ◽  
Gene Encoding ◽  
Independent Manner ◽  
Toxin Gene Expression

ABSTRACT Expression of the structural genes for the anthrax toxin proteins is coordinately controlled by host-related signals, such as elevated CO2, and the trans-acting positive regulator AtxA. In addition to these requirements, toxin gene expression is under growth phase regulation. The transition state regulator AbrB represses atxA expression to influence toxin synthesis. During the late exponential phase of growth, when AbrB levels begin to decrease, toxin synthesis increases. Here we report that toxin gene expression also requires the presence of sigH, a gene encoding the RNA polymerase sigma factor associated with development in Bacillus subtilis. In the well-studied B. subtilis system, σH is required for sporulation and other post-exponential-phase processes and is part of a feedback control pathway for abrB expression. Our data indicate that a Bacillus anthracis sigH-null mutant is asporogenous and toxin deficient. Yet the sigma factor is required for toxin gene expression in a manner that is independent of the pathway leading to post-exponential-phase gene expression. σH positively controls atxA in an AbrB-independent manner. These findings, combined with previous observations, suggest that the steady-state level of atxA expression is critical for optimal toxin gene transcription. We propose a model whereby, under toxin-inducing growth conditions, control of toxin gene expression is fine-tuned by the independent effects of σH and AbrB on the expression of atxA.

Regulation of toxin gene expression in Clostridium perfringens

2015 ◽  
Vol 166 (4) ◽  
pp. 280-289 ◽  
Author(s):  
Kaori Ohtani ◽  
Tohru Shimizu
Keyword(s):  
Gene Expression ◽  
Clostridium Perfringens ◽  
Toxin Gene ◽  
Toxin Gene Expression

scholarly journals RstA Is a Major Regulator ofClostridioides difficileToxin Production and Motility

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Adrianne N. Edwards ◽  
Brandon R. Anjuwon-Foster ◽  
Shonna M. McBride
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Toxin Production ◽  
Toxin Gene ◽  
Dna Binding Domain ◽  
Content Type ◽  
Toxin Genes ◽  
Clostridioides Difficile ◽  
Species Specific ◽  
Toxin Gene Expression

ABSTRACTClostridioides difficileinfection (CDI) is a toxin-mediated diarrheal disease. Several factors have been identified that influence the production of the two majorC. difficiletoxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified aC. difficileregulator, RstA, that promotes sporulation and represses motility and toxin production. We observed that the predicted DNA-binding domain of RstA was required for RstA-dependent repression of toxin genes, motility genes, andrstAtranscription. In this study, we further investigated the regulation of toxin and motility gene expression by RstA. DNA pulldown assays confirmed that RstA directly binds therstApromoter via the predicted DNA-binding domain. Through mutational analysis of therstApromoter, we identified several nucleotides that are important for RstA-dependent transcriptional regulation. Further, we observed that RstA directly binds and regulates the promoters of the toxin genestcdAandtcdB, as well as the promoters for thesigDandtcdRgenes, which encode regulators of toxin gene expression. Complementation analyses with theClostridium perfringensRstA ortholog and a multispecies chimeric RstA protein revealed that theC. difficileC-terminal domain is required for RstA DNA-binding activity, suggesting that species-specific signaling controls RstA function. Our data demonstrate that RstA is a transcriptional repressor that autoregulates its own expression and directly inhibits transcription of the two toxin genes and two positive toxin regulators, thereby acting at multiple regulatory points to control toxin production.IMPORTANCEClostridioides difficileis an anaerobic, gastrointestinal pathogen of humans and other mammals.C. difficileproduces two major toxins, TcdA and TcdB, which cause the symptoms of the disease, and forms dormant endospores to survive the aerobic environment outside the host. A recently discovered regulatory factor, RstA, inhibits toxin production and positively influences spore formation. Herein, we determine that RstA directly binds its own promoter DNA to repress its own gene transcription. In addition, our data demonstrate that RstA directly represses toxin gene expression and gene expression of two toxin gene activators, TcdR and SigD, creating a complex regulatory network to tightly control toxin production. This study provides a novel regulatory link betweenC. difficilesporulation and toxin production. Further, our data suggest thatC. difficiletoxin production is regulated through a direct, species-specific sensing mechanism.

scholarly journals Quantification of Cell Proliferation and Alpha-Toxin Gene Expression of Clostridium perfringens in the Development of Necrotic Enteritis in Broiler Chickens

2007 ◽  
Vol 73 (21) ◽  
pp. 7110-7113 ◽  
Author(s):  
Weiduo Si ◽  
Joshua Gong ◽  
Yanming Han ◽  
Hai Yu ◽  
John Brennan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Regression Model ◽  
Clostridium Perfringens ◽  
Broiler Chickens ◽  
Toxin Gene ◽  
Necrotic Enteritis ◽  
Lesion Score ◽  
Alpha Toxin ◽  
Toxin Gene Expression

ABSTRACT Cell proliferation and alpha-toxin gene expression of Clostridium perfringens in relation to the development of necrotic enteritis (NE) were investigated. Unlike bacitracin-treated chickens, non-bacitracin-treated birds exhibited typical NE symptoms and reduced growth performance. They also demonstrated increased C. perfringens proliferation and alpha-toxin gene expression that were positively correlated and progressed according to the regression model y = b 0 + b 1 X − b 2 X 2. The average C. perfringens count of 5 log10 CFU/g in the ileal digesta appears to be a threshold for developing NE with a lesion score of 2.

scholarly journals Repression of Clostridium difficile toxin gene expression by CodY

2007 ◽  
Vol 66 (1) ◽  
pp. 206-219 ◽  
Author(s):  
Sean S. Dineen ◽  
Anuradha C. Villapakkam ◽  
Jared T. Nordman ◽  
Abraham L. Sonenshein
Keyword(s):  
Gene Expression ◽  
Clostridium Difficile ◽  
Toxin Gene ◽  
Clostridium Difficile Toxin ◽  
Toxin Gene Expression

scholarly journals atxA Controls Bacillus anthracis Capsule Synthesis via acpA and a Newly Discovered Regulator, acpB

2004 ◽  
Vol 186 (2) ◽  
pp. 307-315 ◽  
Author(s):  
Melissa Drysdale ◽  
Agathe Bourgogne ◽  
Susan G. Hilsenbeck ◽  
Theresa M. Koehler
Keyword(s):  
Gene Expression ◽  
Bacillus Anthracis ◽  
Gene Transcription ◽  
Double Mutant ◽  
Regulatory Proteins ◽  
Toxin Gene ◽  
Virulence Plasmid ◽  
Predicted Amino Acid Sequence ◽  
Null Mutant ◽  
Virulence Plasmids

ABSTRACT Two regulatory genes, acpA and atxA, have been reported to control expression of the Bacillus anthracis capsule biosynthesis operon capBCAD. The atxA gene is located on the virulence plasmid pXO1, while pXO2 carries acpA and the cap genes. acpA has been viewed as the major regulator of the cap operon because it is essential for capsule gene expression in a pXO1− pXO2+ strain. atxA is essential for toxin gene transcription but has also been implicated in control of the cap genes. The molecular functions of the regulatory proteins are unknown. We examined cap gene expression in a genetically complete pXO1+ pXO2+ strain. Our results indicate that another pXO2 gene, acpB (previously called pXO2-53; accession no. NC002146.1 :49418-50866), has a role in cap expression. The predicted amino acid sequence of AcpB is 62% similar to that of AcpA and 50% similar to that of AtxA. Assessment of cap gene transcription revealed that cap expression was not affected in a pXO1+ pXO2+ acpB-null mutant and was slightly reduced in an isogenic acpA mutant. However, cap gene expression was abolished in an acpA acpB double mutant. Microscopic examination of capsule synthesis by the mutants corroborated these findings. acpA and acpB expression is controlled by atxA; capsule synthesis and transcription of acpA and acpB were markedly reduced in an atxA mutant. The data suggest that, in a strain containing both virulence plasmids, atxA is the major regulator of capsule synthesis and controls capBCAD expression indirectly, via positive regulation of acpA and acpB.

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