Helicobacter pylori : molecular mechanisms for the utilization of the cell surface as a replicative niche
- Helicobacter pylori is a bacterium that chronically infects the stomachs of more than half the human population, in some cases leading to serious diseases such as gastric cancer and ulcers. H. pylori intimately interact with the gastric epithelial surface, but much remains unknown about its life on the cell surface. The bacterium possesses several tools for its close interaction with the gastric epithelia, including a type IV secretion system, through which the virulence factor CagA is directly translocated into host cells. This dissertation focuses on how H. pylori's close interactions with the epithelial cells allows it to modify the apical cell surface to turn it into a replicative niche for the bacterium. Using live-cell microscopy to follow the fate of individual bacteria on the cell surface, we find that H. pylori is able to utilize the apical cell surface as a replicative niche, even in conditions that do not support the growth of free-swimming bacteria. Experiments with a polarized epithelial model system show that the bacterium's major virulence factors CagA and VacA both play important roles in enabling H. pylori growth and microcolony formation on the apical cell surface, by mediating perturbation of host cell polarity and intracellular trafficking processes. We find that iron is one important micronutrient that H. pylori acquires from host cells during colonization of the polarized epithelium. CagA and VacA act in concert to affect the polarized process of transferrin/transferrin receptor recycling and iron uptake in the host cells, resulting in the mis-sorting of a subset of the transferrin/transferrin receptor complex to the colonizing bacteria on the apical cell surface. This process is functionally important for the bacteria, as downregulation of transferrin receptor expression resulted in a decreased ability of H. pylori to colonize the polarized epithelium. These studies establish the cell surface as a replicative niche, which presents challenges that require bacterial adaptation for its successful utilization. Our findings also illustrate the concept that contact-dependent bacterial virulence factors may be used for the perturbation of host cell physiology for the bacterium's benefit, allowing acquisition of needed factors directly from host cells, and colonization of the apical cell surface.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|2010, c2011; 2010
|Stanford University, Department of Microbiology and Immunology
|Nelson, W. J. (W. James)
|Nelson, W. J. (W. James)
|Statement of responsibility
|Submitted to the Department of Microbiology and Immunology.
|Thesis (Ph.D.)--Stanford University, 2011.
- © 2011 by Shumin Tan
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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