Regulation of Toxin Delivery System and other Genes of Helicobacter pylori on Adherence to the Human Gastric Cell Line
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Regulation of Toxin Delivery System and other Genes of Helicobacter pylori on Adherence to the Human Gastric Cell Line
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| Creator |
Baidya, Amit K
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| Subject |
Infectious Diseases and Immunology
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| Description |
Helicobacter pylori is a gram negative, spiral shaped bacteria persistently colonizes the gastric mucosa of approximately one half of the world’s population leading to chronic gastric inflammation, peptic ulcer disease, gastric cancer or MALT lymphoma in some individuals. The major toxins of H. pylori are CagA and VacA. CagA is encoded by cagA gene of ~40kb Cag pathogenicity island (Cag-PAI). Motility and chemotaxis is the major factor for H. pylori to colonize the human stomach as strains deficient in many flagellar biosynthesis genes are not competent to colonize. Adherence of H. pylori to the gastric epithelial cell line AGS strongly induces expression of the major virulence gene cagA. In this study, we demonstrate that cagA upregulation in AGS-adhered H. pylori is dependent on the flagellar hook-length control protein FliK. The fliK gene was strongly induced in AGS-adhered H. pylori and practically no upregulation of cagA was observed in a fliK mutant following adherence to AGS cells. In a ΔfliK mutant, the anti- σ28 factor FlgM sequesters σ28 within the cell and the concentration of free, functional σ28 is lower in the ΔfliK mutant than in the wild type strain. To examine whether σ28 had a role in cagA upregulation in AGS-adhered H. pylori, a fliA mutant deficient in 28 was constructed. Using the fliA mutant it was shown that cagA upregulation in AGSadhered H. pylori was mediated by 28-RNAP that initiates transcription from a putative promoter downstream of the designated 80-RNAP promoter. Direct binding of 28 to the cagA promoter was demonstrated by chromatin immunoprecipitation and the transcription start site was identified by 5RACE. The 28-dependent cagA promoter was active specifically in AGS-adhered H. pylori. These results indicate that H. pylori has evolved to integrate expression of the major virulence gene cagA with the flagellar regulatory circuit, essential for colonization of the human host.
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| Date |
2014
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2084/1/PhD_THESIS__AMIT_KR_BAIDYA.pdf
Baidya, Amit K (2014) Regulation of Toxin Delivery System and other Genes of Helicobacter pylori on Adherence to the Human Gastric Cell Line. PhD thesis, Calcutta University. |
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| Relation |
http://www.eprints.iicb.res.in/2084/
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