title: Shigella flexneri regulates tight junction-associated proteins in human intestinal epithelial cells.
abstract: Shigella spp. are a group of Gram-negative enteric bacilli that cause acute dysentery in humans. We demonstrate that Shigella flexneri has evolved the ability to regulate functional components of tight junctions after interaction at the apical and basolateral pole of model intestinal epithelia. In the regulation of tight junctional protein assemblies, S. flexneri can engage serotype-specific mechanisms, which targets not only expression, but also cellular distribution and membrane association of components of tight junctions. Distinct mechanisms resulting in the regulation of tight junction-associated proteins are initiated after either apical or basolateral interactions. S. flexneri serotype 2a has the ability to remove claudin-1 from Triton X-insoluble protein fractions upon apical exposure to T-84 cell monolayers. S. flexneri serotype 2a and 5, but not the non-invasive Escherichia coli strain F-18, share the ability to regulate expression of ZO-1, ZO-2, E-cadherin and to dephosphorylate occludin. The disruption of tight junctions is dependent on direct interaction of living Shigella with intestinal epithelial cells and is supported by heat-stable secreted bacterial products. Intestinal epithelial cells have the ability to compensate in part for S. flexneri induced regulation of tight junction-associated proteins.
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease.
authors.forename: Takanori
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Henrik
authors.initials: H
authors.lastname: Köhler
authors.forename: Xiubin
authors.initials: X
authors.lastname: Gu
authors.forename: Beth A
authors.initials: BA
authors.lastname: McCormick
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
mesh_terms: D015820:Cadherins / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D062445:Claudin-1; D015536:Down-Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000502:physiology; D012763:Shigella flexneri / Q000145:classification / Q000502:physiology*; D013045:Species Specificity; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
chemical_list: C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D011506:Proteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein