Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells

Jessica H. Tonry, Beth A. Mcnichol, Nalini Ramarao, Daniel S. Chertow, Kwang Sik Kim, Scott Stibitz, Olaf Schneewind, Fatah Kashanchi, Charles L. Bailey, Serguei Popov, Myung Chul Chung

Research output: Contribution to journalArticle

Abstract

To achieve widespread dissemination in the host, Bacillus anthracis cells regulate their attachment to host endothelium during infection. Previous studies identified BslA (Bacillus anthracisS-layer Protein A), a virulence factor of B.anthracis, as necessary and sufficient for adhesion of vegetative cells to human endothelial cells. While some factors have been identified, bacteria-specific contributions to BslA mediated adhesion remain unclear. Using the attenuated vaccine Sterne 7702 strain of B.anthracis, we tested the hypothesis that InhA (immune inhibitor A), a B.anthracis protease, regulates BslA levels affecting the bacteria's ability to bind to endothelium. To test this, a combination of inhA mutant and complementation analysis in adhesion and invasion assays, Western blot and InhA inhibitor assays were employed. Results show InhA downregulates BslA activity reducing B.anthracis adhesion and invasion in human brain endothelial cells. BslA protein levels in ΔinhA bacteria were significantly higher than wild-type and complemented strains showing InhA levels and BslA expression are inversely related. BslA was sensitive to purified InhA degradation in a concentration- and time-dependent manner. Taken together these data support the role of InhA regulation of BslA-mediated vegetative cell adhesion and invasion.

Original languageEnglish (US)
Pages (from-to)1219-1230
Number of pages12
JournalCellular Microbiology
Volume14
Issue number8
DOIs
StatePublished - Aug 2012

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Bacillus anthracis
Protease Inhibitors
Endothelial Cells
Bacteria
Cell Adhesion
Endothelium
Attenuated Vaccines
Staphylococcal Protein A
Virulence Factors
Bacillus
immune inhibitor A
Peptide Hydrolases
Down-Regulation
Western Blotting
Brain
Infection
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Tonry, J. H., Mcnichol, B. A., Ramarao, N., Chertow, D. S., Kim, K. S., Stibitz, S., ... Chung, M. C. (2012). Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells. Cellular Microbiology, 14(8), 1219-1230. https://doi.org/10.1111/j.1462-5822.2012.01791.x

Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells. / Tonry, Jessica H.; Mcnichol, Beth A.; Ramarao, Nalini; Chertow, Daniel S.; Kim, Kwang Sik; Stibitz, Scott; Schneewind, Olaf; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei; Chung, Myung Chul.

In: Cellular Microbiology, Vol. 14, No. 8, 08.2012, p. 1219-1230.

Research output: Contribution to journalArticle

Tonry, JH, Mcnichol, BA, Ramarao, N, Chertow, DS, Kim, KS, Stibitz, S, Schneewind, O, Kashanchi, F, Bailey, CL, Popov, S & Chung, MC 2012, 'Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells', Cellular Microbiology, vol. 14, no. 8, pp. 1219-1230. https://doi.org/10.1111/j.1462-5822.2012.01791.x
Tonry, Jessica H. ; Mcnichol, Beth A. ; Ramarao, Nalini ; Chertow, Daniel S. ; Kim, Kwang Sik ; Stibitz, Scott ; Schneewind, Olaf ; Kashanchi, Fatah ; Bailey, Charles L. ; Popov, Serguei ; Chung, Myung Chul. / Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells. In: Cellular Microbiology. 2012 ; Vol. 14, No. 8. pp. 1219-1230.
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