Multipronged regulatory functions of a novel endonuclease (TieA) fromHelicobacter pylori
| Autor: | Savita Devi, Niyaz Ahmed, Shivendra Tenguria, Naveen Kumar, Suhail A. Ansari |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Virulence Apoptosis Bacterial Adhesion Helicobacter Infections Microbiology Type IV Secretion Systems 03 medical and health sciences Bacterial Proteins Cell Line Tumor Genetics Cluster Analysis Humans Secretion fas Receptor Transcription factor Helicobacter pylori biology Nucleic Acid Enzymes Kinase Gene Expression Profiling Hydrolysis Immune Sera Macrophages Gene Expression Regulation Bacterial Hydrogen-Ion Concentration Endonucleases biology.organism_classification Antibodies Bacterial Immunity Innate 030104 developmental biology Secretory protein Gastric Mucosa Host-Pathogen Interactions Mutation Cytokine secretion Mitogen-Activated Protein Kinases Gene Deletion Genome Bacterial Protein Binding |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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