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The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β1 receptor results in injection of the CagA oncoprotein. However, the apical surface of epithelial cells is exposed to Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA delivery into polarized gastric epithelial cells remains enigmatic. Here, we demonstrate that T4SS pilus formation during infection of polarized cells occurs predominantly at basolateral membranes, and not at apical sites. Hp accomplishes this by secreting another bacterial protein, the serine protease HtrA, which opens cell-to-cell junctions through cleaving epithelial junctional proteins including occludin, claudin-8, and E-cadherin. Using a genetic system expressing a peptide inhibitor, we demonstrate that HtrA activity is necessary for paracellular transmigration of Hp across polarized cell monolayers to reach basolateral membranes and inject CagA. The contribution of this unique signaling cascade to Hp pathogenesis is discussed.
Pubmed ID: 29024645 RIS Download
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This monoclonal targets Integrin, beta-1 subunit
View all literature mentionsThis unknown targets Helicobacter pylori Cag antigen polyclonal antibody
View all literature mentionsThis unknown targets HA
View all literature mentionsThis polyclonal targets CDH1
View all literature mentionsThis recombinant polyclonal targets Claudin 8
View all literature mentionsThis unknown targets Occludin
View all literature mentionsThis monoclonal targets E-Cadherin
View all literature mentionsThis monoclonal targets p-Tyr (PY99)
View all literature mentionsThis unknown targets Helicobacter pylori Cag antigen monoclonal antibody
View all literature mentionsCell line MKN28 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-N87 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsIn vivo imaging software which facilitates workflow for in vivo optical, X-ray and microCT image acquisition, analysis and data organization.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsCell line MDCK is a Spontaneously immortalized cell line with a species of origin Canis lupus familiaris
View all literature mentionsCell line AGS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Integrin, beta-1 subunit
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