title: Multipronged regulatory functions of a novel endonuclease (TieA) from Helicobacter pylori.
abstract: Helicobacter pylori portrays a classical paradigm of persistent bacterial infections. A well balanced homeostasis of bacterial effector functions and host responses is purported to be the key in achieving long term colonization in specific hosts. H. pylori nucleases have been shown to assist in natural transformation, but their role in virulence and colonization remains elusive. Therefore, it is imperative to understand the involvement of these nucleases in the pathogenesis of H. pylori Here, we report the multifaceted role of a TNFR-1 interacting endonuclease A (TieA) from H. pylori. tieA expression is differentially regulated in response to environmental stress and post adherence to gastric epithelial cells. Studies with isogenic knockouts of tieA revealed it to be a secretory protein which translocates into the host gastric epithelial cells independent of a type IV secretion system, gets phosphorylated by DNA-PK kinase and auto-phosphorylates as serine kinase. Furthermore, TieA binds to and cleaves DNA in a non-specific manner and promotes Fas mediated apoptosis in AGS cells. Additionally, TieA induced pro-inflammatory cytokine secretion via activation of transcription factor AP-1 and signaled through MAP kinase pathway. Collectively, TieA with its multipronged and moonlighting functions could facilitate H. pylori in maintaining a balance of bacterial adaptation, and elimination by the host responses.
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad 500046, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Devi
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad 500046, India.
authors.forename: Suhail A
authors.initials: SA
authors.lastname: Ansari
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad 500046, India.
authors.forename: Shivendra
authors.initials: S
authors.lastname: Tenguria
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad 500046, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad 500046, India ahmed.nizi@gmail.com.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004720:Endonucleases / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007106:Immune Sera / Q000276:immunology; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D000069319:Type IV Secretion Systems; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007106:Immune Sera; D000069319:Type IV Secretion Systems; D019014:fas Receptor; D020928:Mitogen-Activated Protein Kinases; D004720:Endonucleases