Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal toxin

R. Sapra, S. P. Gaucher, J. S. Lachmann, G. M. Buffleben, G. S. Chirica, Jason Comer, Johnny Peterson, Ashok Chopra, A. K. Singh

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Bacillus anthracis is the etiological agent of anthrax and the bacterium produces a tripartite anthrax toxin composed of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA represents the binding domain of the toxin and acts in concert with either LF, a metalloprotease, or EF, an adenylate cyclase, to form lethal toxin (LeTx) or edema toxin (EdTx), respectively. We analyzed the proteomics response of two murine macrophage cell lines (J774.1A and RAW264.7) following B. anthracis LeTx treatment to detect unique host proteins involved in anthrax infection using difference in-gel electrophoresis (DIGE) followed by nanoLC-MS for identification of the proteins. The comparative proteomics approach identified a set of proteins in each cell line that was consistently upregulated when the two macrophage cell lines were treated with LeTx. The upregulated proteins include those involved in energy metabolism, cytoskeleton structure and stress response. A subset of five proteins (ATP synthase β subunit, β-actin, Hsp70, vimentin, and Hsp60 homolog) was identified that were commonly upregulated in both cell lines. The proteomic data suggest the involvement of reactive oxygen species (ROS) in cell lysis as seen by the upregulation of proteins that lead to the production of ROS in both the cell lines used in our study. However, proteins that afford protection against ROS may play an important role in the survival of the macrophage to LeTx infection as shown by the differences in proteomic responses of the two cell lines to the action of LeTx. These identified proteins may have the potential to be used as biomarkers for diagnostics and therapeutics.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalMicrobial Pathogenesis
Volume41
Issue number4-5
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Proteomics
Macrophages
Cell Line
Proteins
Reactive Oxygen Species
Anthrax
Antigens
Bacillus anthracis
anthrax toxin
Metalloproteases
Vimentin
Infection
Cytoskeleton
Adenylyl Cyclases
Energy Metabolism
Electrophoresis
Actins
Edema
Up-Regulation
Adenosine Triphosphate

Keywords

  • Bacillus anthracis
  • Difference in-gel electrophoresis (DIGE)
  • Lethal toxin
  • Macrophage cell lines
  • Reactive oxygen species (ROS)

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Sapra, R., Gaucher, S. P., Lachmann, J. S., Buffleben, G. M., Chirica, G. S., Comer, J., ... Singh, A. K. (2006). Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal toxin. Microbial Pathogenesis, 41(4-5), 157-167. https://doi.org/10.1016/j.micpath.2006.07.002

Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal toxin. / Sapra, R.; Gaucher, S. P.; Lachmann, J. S.; Buffleben, G. M.; Chirica, G. S.; Comer, Jason; Peterson, Johnny; Chopra, Ashok; Singh, A. K.

In: Microbial Pathogenesis, Vol. 41, No. 4-5, 10.2006, p. 157-167.

Research output: Contribution to journalArticle

Sapra, R, Gaucher, SP, Lachmann, JS, Buffleben, GM, Chirica, GS, Comer, J, Peterson, J, Chopra, A & Singh, AK 2006, 'Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal toxin', Microbial Pathogenesis, vol. 41, no. 4-5, pp. 157-167. https://doi.org/10.1016/j.micpath.2006.07.002
Sapra R, Gaucher SP, Lachmann JS, Buffleben GM, Chirica GS, Comer J et al. Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal toxin. Microbial Pathogenesis. 2006 Oct;41(4-5):157-167. https://doi.org/10.1016/j.micpath.2006.07.002
Sapra, R. ; Gaucher, S. P. ; Lachmann, J. S. ; Buffleben, G. M. ; Chirica, G. S. ; Comer, Jason ; Peterson, Johnny ; Chopra, Ashok ; Singh, A. K. / Proteomic analyses of murine macrophages treated with Bacillus anthracis lethal toxin. In: Microbial Pathogenesis. 2006 ; Vol. 41, No. 4-5. pp. 157-167.
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