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Title page for ETD etd-11222011-140044

Type of Document Dissertation
Author Shaffer, Carrie Leigh
URN etd-11222011-140044
Title Role of unique Helicobacter pylori proteins in the Cag pathogenicity island-encoded type IV secretion system
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
D. Borden Lacy Committee Chair
Andrew Link Committee Member
Eric Skaar Committee Member
Roy Zent Committee Member
Seth Bordenstein Committee Member
Timothy Cover Committee Member
  • bacteriology
  • proteomics
  • Helicobacter pylori
  • pathogenicity
Date of Defense 2011-10-13
Availability unrestricted
Colonization of the human stomach by Helicobacter pylori is an important risk factor for development of gastric cancer. The H. pylori cag pathogenicity island (cag PAI) encodes components of a type IV secretion system (T4SS) that translocates the bacterial oncoprotein CagA into gastric epithelial cells, and CagL is a specialized component of the cag T4SS that binds the host receptor α5β1 integrin. Herein, we describe a mass spectrometry-based approach to identify a T4SS subassembly that contains CagL, CagH, and CagI. We demonstrate that these three proteins are required for CagA translocation into host cells and H. pylori-induced IL-8 secretion by gastric epithelial cells; however, these proteins are not homologous to components of T4SSs in other bacterial species. Moreover, we show that these proteins play key roles in biogenesis of T4SS pili at the bacteria-host cell interface. Collectively, these results highlight the important role played by unique constituents of the H. pylori cag T4SS, and illustrate the marked variation that exists among bacterial T4SSs.
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