Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin

Hoy B, Geppert T, Boehm M, Reisen F, Plattner P, Gadermaier G, Sewald N, Ferreira F, Briza P, Schneider G, Backert S, et al. (2012)
Journal of Biological Chemistry 287(13): 10115-10120.

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Abstract / Bemerkung
The periplasmic chaperone and serine protease HtrA is important for bacterial stress responses and protein quality control. Recently, we discovered that HtrA from Helicobacter pylori is secreted and cleaves E-cadherin to disrupt the epithelial barrier, but it remained unknown whether this maybe a general virulence mechanism. Here, we show that important other pathogens including enteropathogenic Escherichia coli, Shigella flexneri, and Campylobacter jejuni, but not Neisseria gonorrhoeae, cleaved E-cadherin on host cells. HtrA deletion in C. jejuni led to severe defects in E-cadherin cleavage, loss of cell adherence, paracellular transmigration, and basolateral invasion. Computational modeling of HtrAs revealed a conserved pocket in the active center exhibiting pronounced proteolytic activity. Differential E-cadherin cleavage was determined by an alanine-to-glutamine exchange in the active center of neisserial HtrA. These data suggest that HtrA-mediated E-cadherin cleavage is a prevalent pathogenic mechanism of multiple Gram-negative bacteria representing an attractive novel target for therapeutic intervention to combat bacterial infections.
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Journal of Biological Chemistry
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287
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13
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10115-10120
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Hoy B, Geppert T, Boehm M, et al. Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin. Journal of Biological Chemistry. 2012;287(13):10115-10120.
Hoy, B., Geppert, T., Boehm, M., Reisen, F., Plattner, P., Gadermaier, G., Sewald, N., et al. (2012). Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin. Journal of Biological Chemistry, 287(13), 10115-10120. doi:10.1074/jbc.C111.333419
Hoy, B., Geppert, T., Boehm, M., Reisen, F., Plattner, P., Gadermaier, G., Sewald, N., Ferreira, F., Briza, P., Schneider, G., et al. (2012). Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin. Journal of Biological Chemistry 287, 10115-10120.
Hoy, B., et al., 2012. Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin. Journal of Biological Chemistry, 287(13), p 10115-10120.
B. Hoy, et al., “Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin”, Journal of Biological Chemistry, vol. 287, 2012, pp. 10115-10120.
Hoy, B., Geppert, T., Boehm, M., Reisen, F., Plattner, P., Gadermaier, G., Sewald, N., Ferreira, F., Briza, P., Schneider, G., Backert, S., Wessler, S.: Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin. Journal of Biological Chemistry. 287, 10115-10120 (2012).
Hoy, Benjamin, Geppert, Tim, Boehm, Manja, Reisen, Felix, Plattner, Patrick, Gadermaier, Gabriele, Sewald, Norbert, Ferreira, Fatima, Briza, Peter, Schneider, Gisbert, Backert, Steffen, and Wessler, Silja. “Distinct Roles of Secreted HtrA Proteases from Gram-negative Pathogens in Cleaving the Junctional Protein and Tumor Suppressor E-cadherin”. Journal of Biological Chemistry 287.13 (2012): 10115-10120.

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