title: Enterohemorrhagic Escherichia coli effector EspL2 induces actin microfilament aggregation through annexin 2 activation.
abstract: Enterohemorrhagic Escherichia coli (EHEC) delivers virulence factors into host cells through the type III secretion system (T3SS) to exert the bacterial pathogenicity. EHEC encodes more than 20 type III secretion system-delivered families of effectors that have different functions at different infectious stages and enable a successful infection. One of them, EspL2, is encoded on the SpLE3 phage-like element in EHEC O157:H7 Sakai and is well conserved among various EHEC strains. Here we show that, after delivery into host cells, EspL2 accumulated under adherent bacteria, as did polymerized F-actin. EspL2-expressing EHEC formed three-dimensional, condensed microcolonies, into which the host cell extended plasma membrane protrusions on an F-actin-rich cytoskeleton. EspL2 bound F-actin-aggregating annexin 2 directly, increasing its activity. In addition, annexin 2 depletion abolished the EspL2-dependent formation of condensed microcolonies and F-actin aggregation. The EspL2-induced pseudopod-like protrusion of the host plasma membrane interacted with and supported colonization by the bacteria, independent of Tir-mediated actin polymerization. Thus, EspL2 supports efficient colonization by increasing annexin 2's ability to aggregate Tir-induced F-actin and by modifying the morphology of the host cell membrane.
authors.affiliation: Division of Applied Bacteriology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyahara
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Ooka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Nakaba
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Tobe
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D017306:Annexin A2 / Q000378:metabolism*; D001422:Bacterial Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology* / Q000648:ultrastructure; D019453:Escherichia coli O157 / Q000502:physiology* / Q000648:ultrastructure; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008855:Microscopy, Electron, Scanning; D011485:Protein Binding; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D029968:Escherichia coli Proteins; D037521:Virulence Factors