title: Yersinia enterocolitica exploits different pathways to accomplish adhesion and toxin injection into host cells.
abstract: The current paradigm suggests that Yersinia enterocolitica (Ye) adheres to host cells via the outer membrane proteins Yersinia adhesin A (YadA) or invasin (Inv) to facilitate injection of Yops by the type III secretion system. In this process Inv binds directly to β1 integrins of host cells while YadA may bind indirectly via extracellular matrix proteins to β1 integrins. Here we challenged this paradigm and investigated the requirements for Yop injection. We demonstrate that Inv- but not YadA-mediated adhesion depends on β1 integrin binding and activation, and that tight adhesion is a prerequisite for Yop injection. By means of novel transgenic cell lines, shRNA approaches and RGD peptides, we found that YadA, in contrast to Inv, may use a broad host cell receptor repertoire for host cell adhesion. In the absence of β1 integrins, YadA mediates Yop injection by interaction with αV integrins in cooperation with yet unknown cofactors expressed by epithelial cells, but not fibroblasts. Electron microscopic and flow chamber studies revealed that a defined intimate contact area between Ye and host cells resulting in adhesion forces resisting shear stress is required for Yop injection. Thus, the indirect binding of YadA to a broad extracellular matrix (ECM) binding host cell receptor repertoire of different cell types makes YadA a versatile tool to ensure Yop injection. In conclusion, given the differential expression of the outer membrane proteins Inv and YadA in the course of Ye infection and differential expression of integrins by various host cell populations, the data demonstrate that Ye is flexibly armed to accomplish Yop injection in different host cell types, a central event in its immune evasion strategy.
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Birgit
authors: B
authors: Keller
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Melanie
authors: M
authors: Mühlenkamp
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Eva
authors: E
authors: Deuschle
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Alexandra
authors: A
authors: Siegfried
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Sara
authors: S
authors: Mössner
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Jessica
authors: J
authors: Schade
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Tanja
authors: T
authors: Griesinger
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Nenad
authors: N
authors: Katava
authors: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors: Christina
authors: C
authors: Braunsdorf
authors: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors: Birgit
authors: B
authors: Fehrenbacher
authors: Max von Pettenkofer-Institut, Ludwig-Maximilians University, Munich, Germany.
authors: Luisa F
authors: LF
authors: Jiménez-Soto
authors: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors: Martin
authors: M
authors: Schaller
authors: Max von Pettenkofer-Institut, Ludwig-Maximilians University, Munich, Germany.
authors: Rainer
authors: R
authors: Haas
authors: Institute of Toxicology, Medical School Hannover, Hannover, Germany.
authors: Harald
authors: H
authors: Genth
authors: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors: Saverio F
authors: SF
authors: Retta
authors: Max Planck Institut für Biochemie, Martinsried, Germany.|Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Germany.
authors: Hannelore
authors: H
authors: Meyer
authors: Max Planck Institut für Biochemie, Martinsried, Germany.
authors: Ralph T
authors: RT
authors: Böttcher
authors: Department of Medicine (Division of Nephrology), Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Roy
authors: R
authors: Zent
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.|Department of Medicine (Division of Nephrology), Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Monika
authors: M
authors: Schütz
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.|German Centre of Infection Research (DZIF), Partner Site Tübingen, Germany.
authors: Ingo B
authors: IB
authors: Autenrieth
authors: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors: Erwin
authors: E
authors: Bohn
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D039564:Integrin alphaV / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008854:Microscopy, Electron; D011485:Protein Binding; D021381:Protein Transport; D015008:Yersinia enterocolitica / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D001427:Bacterial Toxins; D039564:Integrin alphaV; D019012:Integrin beta1; C064832:YadA protein, Yersinia; C053476:invasin, Yersinia