Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion

Hoy B, Loewer M, Weydig C, Carra G, Tegtmeyer N, Geppert T, Schroeder P, Sewald N, Backert S, Schneider G, Wessler S (2010)
EMBO REPORTS 11(10): 798-804.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ; ; ; ; ; ; ; ; ;
Abstract / Bemerkung
Mammalian and prokaryotic high-temperature requirement A (HtrA) proteins are chaperones and serine proteases with important roles in protein quality control. Here, we describe an entirely new function of HtrA and identify it as a new secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of the cell-adhesion protein E-cadherin. E-cadherin shedding disrupts epithelial barrier functions allowing H. pylori designed to access the intercellular space. We then designed a small-molecule inhibitor that efficiently blocks HtrA activity, E-cadherin cleavage and intercellular entry of H. pylori.
Stichworte
Erscheinungsjahr
Zeitschriftentitel
EMBO REPORTS
Band
11
Zeitschriftennummer
10
Seite
798-804
ISSN
eISSN
PUB-ID

Zitieren

Hoy B, Loewer M, Weydig C, et al. Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO REPORTS. 2010;11(10):798-804.
Hoy, B., Loewer, M., Weydig, C., Carra, G., Tegtmeyer, N., Geppert, T., Schroeder, P., et al. (2010). Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO REPORTS, 11(10), 798-804. doi:10.1038/embor.2010.114
Hoy, B., Loewer, M., Weydig, C., Carra, G., Tegtmeyer, N., Geppert, T., Schroeder, P., Sewald, N., Backert, S., Schneider, G., et al. (2010). Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO REPORTS 11, 798-804.
Hoy, B., et al., 2010. Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO REPORTS, 11(10), p 798-804.
B. Hoy, et al., “Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion”, EMBO REPORTS, vol. 11, 2010, pp. 798-804.
Hoy, B., Loewer, M., Weydig, C., Carra, G., Tegtmeyer, N., Geppert, T., Schroeder, P., Sewald, N., Backert, S., Schneider, G., Wessler, S.: Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO REPORTS. 11, 798-804 (2010).
Hoy, Benjamin, Loewer, Martin, Weydig, Christiane, Carra, Gert, Tegtmeyer, Nicole, Geppert, Tim, Schroeder, Peter, Sewald, Norbert, Backert, Steffen, Schneider, Gisbert, and Wessler, Silja. “Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion”. EMBO REPORTS 11.10 (2010): 798-804.

97 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

From Virtual Screening to Bioactive Compounds by Visualizing and Clustering of Chemical Space.
Klenner A, Hähnke V, Geppert T, Schneider P, Zettl H, Haller S, Rodrigues T, Reisen F, Hoy B, Schaible AM, Werz O, Wessler S, Schneider G., Mol Inform 31(1), 2012
PMID: 27478174
Helicobacter pylori defense against oxidative attack.
Stent A, Every AL, Sutton P., Am J Physiol Gastrointest Liver Physiol 302(6), 2012
PMID: 22194421
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, Wessler S., J Biol Chem 287(13), 2012
PMID: 22337879
the active site residue V266 of Chlamydial HtrA is critical for substrate binding during both in vitro and in vivo conditions.
Gloeckl S, Tyndall JD, Stansfield SH, Timms P, Huston WM., J Mol Microbiol Biotechnol 22(1), 2012
PMID: 22353774
A role for altered phagosome maturation in the long-term persistence of Helicobacter pylori infection.
Borlace GN, Keep SJ, Prodoehl MJ, Jones HF, Butler RN, Brooks DA., Am J Physiol Gastrointest Liver Physiol 303(2), 2012
PMID: 22575220
Bacterial outer membrane vesicles in disease and preventive medicine.
Unal CM, Schaar V, Riesbeck K., Semin Immunopathol 33(5), 2011
PMID: 21153593
Protein quality control in the bacterial periplasm.
Merdanovic M, Clausen T, Kaiser M, Huber R, Ehrmann M., Annu Rev Microbiol 65(), 2011
PMID: 21639788
HTRA proteases: regulated proteolysis in protein quality control.
Clausen T, Kaiser M, Huber R, Ehrmann M., Nat Rev Mol Cell Biol 12(3), 2011
PMID: 21326199
Context-based identification of protein-protein interfaces and "hot-spot" residues.
Geppert T, Hoy B, Wessler S, Schneider G., Chem Biol 18(3), 2011
PMID: 21439479
Inhibitors of Helicobacter pylori protease HtrA found by 'virtual ligand' screening combat bacterial invasion of epithelia.
Löwer M, Geppert T, Schneider P, Hoy B, Wessler S, Schneider G., PLoS One 6(3), 2011
PMID: 21483848
Structure-Based Pharmacophores for Virtual Screening.
Löwer M, Proschak E., Mol Inform 30(5), 2011
PMID: 27467085
HtrA is a major virulence determinant of Bacillus anthracis.
Chitlaru T, Zaide G, Ehrlich S, Inbar I, Cohen O, Shafferman A., Mol Microbiol 81(6), 2011
PMID: 21801240
Pathogenesis of Helicobacter pylori infection.
Backert S, Clyne M., Helicobacter 16 Suppl 1(), 2011
PMID: 21896081
"Targeted disruption of the epithelial-barrier by Helicobacter pylori".
Wroblewski LE, Peek RM., Cell Commun Signal 9(1), 2011
PMID: 22044698
Protease-activated receptor-2 (PAR2) in human gastric mucosa as mediator of proinflammatory effects in Helicobacter pylori infection.
Kandulski A, Kuester D, Mönkemüller K, Fry L, Malfertheiner P, Wex T., Helicobacter 16(6), 2011
PMID: 22059396

23 References

Daten bereitgestellt von Europe PubMed Central.

Basic local alignment search tool.
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ., J. Mol. Biol. 215(3), 1990
PMID: 2231712
Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA.
Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S., Science 300(5624), 2003
PMID: 12775840
E-cadherin in gastric cancer.
Chan AO., World J. Gastroenterol. 12(2), 2006
PMID: 16482618
Helicobacter pylori VacA, a paradigm for toxin multifunctionality.
Cover TL, Blanke SR., Nat. Rev. Microbiol. 3(4), 2005
PMID: 15759043
The role of human HtrA1 in arthritic disease.
Grau S, Richards PJ, Kerr B, Hughes C, Caterson B, Williams AS, Junker U, Jones SA, Clausen T, Ehrmann M., J. Biol. Chem. 281(10), 2006
PMID: 16377621
Proteases in bacterial pathogenesis.
Ingmer H, Brondsted L., Res. Microbiol. 160(9), 2009
PMID: 19778606
Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins.
Jiang J, Zhang X, Chen Y, Wu Y, Zhou ZH, Chang Z, Sui SF., Proc. Natl. Acad. Sci. U.S.A. 105(33), 2008
PMID: 18697939
Structural basis for the regulated protease and chaperone function of DegP.
Krojer T, Sawa J, Schafer E, Saibil HR, Ehrmann M, Clausen T., Nature 453(7197), 2008
PMID: 18496527
Prediction of extracellular proteases of the human pathogen Helicobacter pylori reveals proteolytic activity of the Hp1018/19 protein HtrA.
Lower M, Weydig C, Metzler D, Reuter A, Starzinski-Powitz A, Wessler S, Schneider G., PLoS ONE 3(10), 2008
PMID: 18946507
ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation.
Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D, Saftig P., Proc. Natl. Acad. Sci. U.S.A. 102(26), 2005
PMID: 15958533
Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli.
Meltzer M, Hasenbein S, Mamant N, Merdanovic M, Poepsel S, Hauske P, Kaiser M, Huber R, Krojer T, Clausen T, Ehrmann M., Res. Microbiol. 160(9), 2009
PMID: 19695325
Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells.
Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, Aburatani H, Akiyama T, Peek RM Jr, Azuma T, Hatakeyama M., Oncogene 26(32), 2007
PMID: 17237808
Intracellular, intercellular, and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by Helicobacter pylori.
Necchi V, Candusso ME, Tava F, Luinetti O, Ventura U, Fiocca R, Ricci V, Solcia E., Gastroenterology 132(3), 2007
PMID: 17383424
Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1.
Noe V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M., J. Cell. Sci. 114(Pt 1), 2001
PMID: 11112695
p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7.
Ogden SR, Wroblewski LE, Weydig C, Romero-Gallo J, O'Brien DP, Israel DA, Krishna US, Fingleton B, Reynolds AB, Wessler S, Peek RM Jr., Mol. Biol. Cell 19(10), 2008
PMID: 18653469
Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin.
Papini E, Satin B, Norais N, de Bernard M, Telford JL, Rappuoli R, Montecucco C., J. Clin. Invest. 102(4), 1998
PMID: 9710450
Helicobacter pylori and gastrointestinal tract adenocarcinomas.
Peek RM Jr, Blaser MJ., Nat. Rev. Cancer 2(1), 2002
PMID: 11902583
Global transposon mutagenesis and essential gene analysis of Helicobacter pylori.
Salama NR, Shepherd B, Falkow S., J. Bacteriol. 186(23), 2004
PMID: 15547264
Ectodomain shedding of E-cadherin and c-Met is induced by Helicobacter pylori infection.
Schirrmeister W, Gnad T, Wex T, Higashiyama S, Wolke C, Naumann M, Lendeckel U., Exp. Cell Res. 315(20), 2009
PMID: 19665015
Molecular mechanisms of epithelial-barrier disruption by Helicobacter pylori.
Wessler S, Backert S., Trends Microbiol. 16(8), 2008
PMID: 18619844
Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation.
Wroblewski LE, Shen L, Ogden S, Romero-Gallo J, Lapierre LA, Israel DA, Turner JR, Peek RM Jr., Gastroenterology 136(1), 2009
PMID: 18996125

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 20814423
PubMed | Europe PMC

Suchen in

Google Scholar