Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion.
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.
Hoy
Benjamin
B
Junior Research Group, Paul-Ehrlich Institute, Langen, Germany.
Löwer
Martin
M
Weydig
Christiane
C
Carra
Gert
G
Tegtmeyer
Nicole
N
Geppert
Tim
T
Schröder
Peter
P
Sewald
Norbert
N
Backert
Steffen
S
Schneider
Gisbert
G
Wessler
Silja
S
D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D037521:Virulence Factors / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D015820:Cadherins; D015815:Cell Adhesion Molecules; D037521:Virulence Factors
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