Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E‐cadherin to disrupt intercellular adhesion |
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| Authors: | Gert Carra Nicole Tegtmeyer Tim Geppert Peter Schröder Norbert Sewald Steffen Backert Silja Wessler |
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| Institution: | 1. Junior Research Group, Paul‐Ehrlich Institute, Langen, Germany;2. School of Biomolecular and Biomedical Sciences, University College Dublin, Dublin, Ireland;3. ETH Zürich, Department of Chemistry and Applied Biosciences, Zürich, Switzerland;4. Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Bielefeld, Germany |
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| Abstract: | 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. |
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| Keywords: | H pylori HtrA E‐cadherin |
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