Activity of the Bacillus anthracis 20 kDa protective antigen component
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12533 | GEO | 2008/08/26
SECONDARY ACCESSION(S): PRJNA112885
REPOSITORIES: GEO
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Project description:Edema factor of anthrax binds to the protective antigen (PA83) which cleaves to PA63 and PA20. The role of PA20 was examined using highthroughput gene expression analysis of human peripheral blood mononuclear cells (PBMC) exposed to PA20. Keywords: Toxicity determination PBMC obtained from different individuals over 6 monthes were incubated with and without rPA20
2008-08-26 | E-GEOD-12533 | biostudies-arrayexpress
Project description:BackgroundAnthrax is caused by Bacillus anthracis that produce two exotoxins, lethal toxin and edema toxin. The lethal toxin is composed of the lethal factor (LF) complexed with the cell binding protective antigen (PA83, 83 kDa). Likewise, the edema factor (EF) binds to the PA83 to form the edema toxin. Once PA83 is bound to the host cell surface, a furin-like protease cleaves the full-length, inactive protein into 63 kDa and 20 kDa antigens (PA63 and PA20). PA63 forms a heptamer and is internalized via receptor mediated endocytosis forming a protease-stable pore, which allows EF and LF to enter the cell and exert their toxic effects.Both proteolytically cleaved protective antigens (PA63 and PA20 fragments) are found in the blood of infected animals. The 63 kDa protective antigen PA63 fragment has been thoroughly studied while little is known about the PA20.MethodsIn this study we examined the role of PA20 using high throughput gene expression analysis of human peripheral blood mononuclear cells (PBMC) exposed to the PA20. We constructed a PA mutant in which a Factor Xa proteolytic recognition site was genetically engineered into the protective antigen PA83 to obtain PA20 using limited digestion of this recombinant PA83 with trypsin.ResultsGlobal gene expression response studies indicated modulation of various immune functions and showed gene patterns indicative of apoptosis via the Fas pathway in a subset of the lymphoid cells. This finding was extended to include observations of increased Caspase-3 enzymatic activity and the identification of increases in the population of apoptotic, but not necrotic cells, based on differential staining methods. We identified a list of approximately 40 inflammatory mediators and heat-shock proteins that were altered similarly upon exposure of PBMC to either rPA20 or B. anthracis spores/vegetative cells.ConclusionThis study shows that the PA20 has an effect on human peripheral blood leukocytes and can induce apoptosis in the absence of other PA components.
| S-EPMC2564935 | biostudies-literature
Project description:The spore forming pathogen Bacillus anthracis is the etiologic agent of anthrax in humans and animals. It cycles through infected hosts as vegetative cells and is eventually introduced into the environment where it generates an endospore resistant to many harsh conditions. The endospores are subsequently ingested by the next host to begin the next cycle. Outbreaks of anthrax occur regularly worldwide in wildlife and livestock, and the potential for human infection exists whenever humans encounter infected animals. It is also possible to encounter intentional releases of anthrax spores, as was the case in October 2001. Consequently, it is important to be able to rapidly establish the provenance of infectious strains of B. anthracis. Here, we compare protein expression in seven low-passage wild isolates and four laboratory strains of B. anthracis grown under identical conditions using LC-MS/MS proteomic analysis. Of the 1,023 total identified proteins, 96 had significant abundance differences between wild and laboratory strains. Of those, 28 proteins directly related to sporulation were upregulated in wild isolates, with expression driven by Spo0A, CodY, and AbrB/ScoC. In addition, we observed evidence of changes in cell division and fatty acid biosynthesis between the two classes of strains, despite being grown under identical experimental conditions. These results suggest wild B. anthracis cells are more highly tuned to sporulate than their laboratory cousins, and this difference should be exploited as a method to differentiate between laboratory adapted cultures and low passage wild strains isolated during an anthrax outbreak. This knowledge should distinguish between intentional releases and exposure to strains in nature providing a basis for the type of response by public health officials and investigators.
2018-12-04 | PXD010120 | Pride
Project description:Anthrax lethal toxin directly targets human peripheral monocytes and causes multiple aberrant gene responses that would be expected to result in defects in human monocyte’s normal signaling transduction pathways and nction. This study provides further insights into the mechanisms associated with the host immune system collapse during an anthrax infection, and suggests that anthrax LT may have additional targets outside the well-known MAPK pathway.
2012-12-12 | GSE34407 | GEO
Project description:Edema toxin (EdTx), which is a combination of edema factor and a binding moiety (protective antigen), is produced by Bacillus anthracis, the etiological agent of anthrax. EdTx is an adenylyl cyclase enzyme that converts adenosine triphosphate to adenosine-3',5'-monophosphate, resulting in interstitial edema seen in anthrax patients. We used GeneChip analysis to examine global transcriptional profiles of EdTx-treated RAW 264.7 murine macrophage-like cells at 3 and 6 hr. Experiment Overall Design: RAW 264.7 cells were treated with EdTx (2.5 µg/ml of protective antigen and 0.625 µg/ml of Edema factor), PA (2.5 µg/ml), or LPS (1 ng/mL) for 0, 3, and 6 hr. Each experiment was performed in triplicate, generating a total of 21 arrays (biological replciates).
2007-11-22 | E-GEOD-4712 | biostudies-arrayexpress
Project description:Bacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP. We used microarrays to decipher the specific gene regulation in edema toxin (ET), the complex of EF and PA, treated mouse bone marrow derived macrophages. Experiment Overall Design: BMDM were treated with 1 mg/ml of ET and the RNAs were purified at 0, 2, and 4h after toxin treatment.
2008-06-16 | E-GEOD-9184 | biostudies-arrayexpress
Project description:Bacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP. We used microarrays to decipher the specific gene regulation in edema toxin (ET), the complex of EF and PA, treated mouse bone marrow derived macrophages. Keywords: Time course
2007-09-28 | GSE9184 | GEO
Project description:Anthrax lethal toxin directly targets human peripheral monocytes and causes multiple aberrant gene responses that would be expected to result in defects in human monocyteM-bM-^@M-^Ys normal signaling transduction pathways and nction. This study provides further insights into the mechanisms associated with the host immune system collapse during an anthrax infection, and suggests that anthrax LT may have additional targets outside the well-known MAPK pathway. There were 4 replicates, 1 control and 1 toxin treated from 4 donors, with 8 samples total. key word : Toxin response
2012-12-12 | E-GEOD-34407 | biostudies-arrayexpress
Project description:Bacillus anthracis causes anthrax infections in mammals. Large-scale mortality resulting from the intentional release of B. anthracis spores represents a potential bioterrorism threat. Inhalational anthrax almost invariably proceeds to fatal systemic infection, characterized by massive bacteremia. A better understanding of host-pathogen interactions is urgently needed for effective treatment of this lethal disease. However, virulence mechanisms used by B. anthracis to survive and multiply in human blood are not completely understood. Identification of genes that are differentially expressed during the growth of B. anthracis in human serum can elucidate how this pathogen successfully colonizes the bloodstream. We compared the transcriptional profile of B. anthracis growing in heat-inactivated human serum to that in LB medium. Genes involved in the biosynthesis of purines, certain amino acids and riboflavin and lipid metabolism, genes encoding ABC transporters, respiratory enzymes and several genes with hypothetical function were identified as being upregulated during growth in serum.
2022-12-01 | GSE97567 | GEO