title: Apically exposed, tight junction-associated beta1-integrins allow binding and YopE-mediated perturbation of epithelial barriers by wild-type Yersinia bacteria.
abstract: Using polarized epithelial cells, primarily MDCK-1, we assessed the mode of binding and effects on epithelial cell structure and permeability of Yersinia pseudotuberculosis yadA-deficient mutants. Initially, all bacteria except the invasin-deficient (inv) mutant adhered apically to the tight junction areas. These contact points of adjacent cells displayed beta1-integrins together with tight junction-associated ZO-1 and occludin proteins. Indeed, beta1-integrin expression was maximal in the tight junction area and then gradually decreased along the basolateral membranes. Wild-type bacteria also opened gradually the tight junction to paracellular permeation of different-sized markers, viz., 20-, 40-, and 70-kDa dextrans and 45-kDa ovalbumin, as well as to their own translocation between adjacent cells in intimate contact with beta1-integrins. The effects on the epithelial cells and their barrier properties could primarily be attributed to expression of the Yersinia outer membrane protein YopE, as the yopE mutant bound but caused no cytotoxicity. Moreover, the apical structure of filamentous actin (F-actin) was disturbed and tight junction-associated proteins (ZO-1 and occludin) were dispersed along the basolateral membranes. It is concluded that the Yersinia bacteria attach to beta1-integrins at tight junctions. Via this localized injection of YopE, they perturb the F-actin structure and distribution of proteins forming and regulating tight junctions. Thereby they promote paracellular translocation of bacteria and soluble compounds.
authors.affiliation: Division of Medical Microbiology, Department of Health and Environment, Linköping University, S-581 85 Linköping, Sweden. farta@mme.liu.se
authors.forename: F
authors.initials: F
authors.lastname: Tafazoli
authors.forename: A
authors.initials: A
authors.lastname: Holmström
authors.forename: A
authors.initials: A
authors.lastname: Forsberg
authors.forename: K E
authors.initials: KE
authors.lastname: Magnusson
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000382:microbiology; D019012:Integrin beta1 / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000032:analysis; D019108:Tight Junctions / Q000502:physiology*; D015011:Yersinia pseudotuberculosis / Q000502:physiology*; D062826:Zonula Occludens-1 Protein
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019012:Integrin beta1; D008565:Membrane Proteins; D062793:Occludin; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; C063239:yopE protein, Yersinia