title: How Shigella Utilizes Ca(2+) Jagged Edge Signals during Invasion of Epithelial Cells.
abstract: Shigella, the causative agent of bacillary dysentery invades intestinal epithelial cells using a type III secretion system (T3SS). Through the injection of type III effectors, Shigella manipulates the actin cytoskeleton to induce its internalization in epithelial cells. At early invasion stages, Shigella induces atypical Ca(2+) responses confined at entry sites allowing local cytoskeletal remodeling for bacteria engulfment. Global Ca(2+) increase in the cell triggers the opening of connexin hemichannels at the plasma membrane that releases ATP in the extracellular milieu, favoring Shigella invasion and spreading through purinergic receptor signaling. During intracellular replication, Shigella regulates inflammatory and death pathways to disseminate within the epithelium. At later stages of infection, Shigella downregulates hemichannel opening and the release of extracellular ATP to dampen inflammatory signals. To avoid premature cell death, Shigella activates cell survival by upregulating the PI3K/Akt pathway and downregulating the levels of p53. Furthermore, Shigella interferes with pro-apoptotic caspases, and orients infected cells toward a slow necrotic cell death linked to mitochondrial Ca(2+) overload. In this review, we will focus on the role of Ca(2+) responses and their regulation by Shigella during the different stages of bacterial infection.
authors.affiliation: Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie, Collège de FranceParis, France; Institut National de la Santé et de la Recherche Médicale U1050Paris, France; Centre National de la Recherche Scientifique, UMR7241Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science LettreParis, France.
authors.forename: Mariette
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie, Collège de FranceParis, France; Institut National de la Santé et de la Recherche Médicale U1050Paris, France; Centre National de la Recherche Scientifique, UMR7241Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science LettreParis, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Tran Van Nhieu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000382:microbiology / Q000473:pathology*; D004847:Epithelial Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008928:Mitochondria / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012760:Shigella / Q000276:immunology* / Q000472:pathogenicity*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D000069296:Type III Secretion Systems / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000069296:Type III Secretion Systems; D000255:Adenosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases
keywords: Ca2+ signaling; Shigella invasion; host cell survival; inflammation; mitochondria-induced cell death