title: Enterohaemorrhagic Escherichia coli requires the spectrin cytoskeleton for efficient attachment and pedestal formation on host cells.
abstract: Recent work has demonstrated that the spectrin cytoskeleton is a host cell target, exploited during intestinal bacterial disease. Here we show that the highly virulent intestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) is also reliant upon the spectrin cytoskeleton during key pathogenic events. Immunofluorescent microscopy demonstrated that the core components of the spectrin cytoskeleton (spectrin, adducin, and protein 4.1 [p4.1]) are recruited to sites of EHEC attachment and localized at pedestal structures along with the EHEC pedestal specific proteins IRSp53 and IRTKS. Further studies involving siRNA-mediated knockdowns of spectrin, adducin, or p4.1 revealed that those proteins are needed for efficient docking of EHEC to host cells, are involved in recruiting IRSp53 to the pedestal and are necessary for pedestal formation. These findings identify the spectrin cytoskeleton as a major host cell cytoskeletal network involved in critical EHEC pathogenic events.
authors.affiliation: Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada.
authors.forename: Tyson Joel
authors.initials: TJ
authors.lastname: Ruetz
authors.forename: Ann En-Ju
authors.initials: AE
authors.lastname: Lin
authors.forename: Julian Andrew
authors.initials: JA
authors.lastname: Guttman
mesh_terms: D001422:Bacterial Adhesion; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054324:Enterohemorrhagic Escherichia coli / Q000472:pathogenicity*; D020868:Gene Silencing; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013049:Spectrin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D013049:Spectrin; D000099291:Adducins; C119539:BAIAP2 protein, human; C523100:BAIAP2L1 protein, human; C078446:protein 4.1 Presles