Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni.
Host cell invasion of the food-borne pathogen Campylobacter jejuni is one of the primary reasons of tissue damage in humans but molecular mechanisms are widely unclear. Here, we show that C. jejuni triggers membrane ruffling in the eukaryotic cell followed by invasion in a very specific manner first with its tip followed by the flagellar end. To pinpoint important signalling events involved in the C. jejuni invasion process, we examined the role of small Rho family GTPases. Using specific GTPase-modifying toxins, inhibitors and GTPase expression constructs we show that Rac1 and Cdc42, but not RhoA, are involved in C. jejuni invasion. In agreement with these observations, we found that internalization of C. jejuni is accompanied by a time-dependent activation of both Rac1 and Cdc42. Finally, we show that the activation of these GTPases involves different host cell kinases and the bacterial fibronectin-binding protein CadF. Thus, CadF is a bifunctional protein which triggers bacterial binding to host cells as well as signalling leading to GTPase activation. Collectively, our results suggest that C. jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 plays a crucial role in this entry process.
Krause-Gruszczynska
Malgorzata
M
Department of Medical Microbiology, Otto von Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Rohde
Manfred
M
Hartig
Roland
R
Genth
Harald
H
Schmidt
Gudula
G
Keo
Thormika
T
König
Wolfgang
W
Miller
William G
WG
Konkel
Michael E
ME
Backert
Steffen
S
D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D016123:Campylobacter jejuni / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005407:Flagella / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008855:Microscopy, Electron, Scanning; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D001425:Bacterial Outer Membrane Proteins; C107872:CadF protein, Campylobacter jejuni; D002352:Carrier Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein