Abstract
[Truncated] Helicobacter pylori has colonized and coevolved with humans for at least 60,000. This prolonged and intimate relationship is likely to have shaped the large and diverse repertoire of strategies that H. pylori employs to establish robust colonization and persist in the gastric niche. H. pylori infection is usually acquired during early childhood and persists lifelong due to the inability of the immune system to clear the bacteria.
Like other Gram-negative bacteria, H. pylori constitutively releases outer membrane vesicles (OMVs) from the surface of the cell envelope both in vitro and in vivo. These 20-250 nm diameter, spherical, and bilayered vesicles are packed with outer membrane proteins (OMPs), peptidoglycan, and lipopolysaccharide(LPS). These vesicles represent an important means of H. pylori host-pathogen interactions as evidenced by their ability to deliver active virulence factors directly to gastric epithelial cells and modulate host immune responses. This study investigated H. pylori OMVs biogenesis from three aspects: the pathogenic molecules assembly, the influence of outer membrane (OM)homeostasis on OMVs formation, and LPS role in OMVs biogenesis.
As a characteristic virulence factor, the sorting signal of vacuolating cytotoxin (VacA) to H. pylori OMVs was investigated based on the 19 vacA gene mutations generated in this study.The results proved that only the VacA mature cytotoxin was released to the extracellular space and existed in both OMVs-associated and free-soluble forms. The study also found that only the oligomeric VacA could be sorted to H. pylori OMVs by attaching to the vesicles surface. Furthermore, the autotransporter character of VacA protein was also exploited for loading heterologous protein to OMVs, which demonstrated the potential for the development of H. Pylori OMVs based vaccines.
Like other Gram-negative bacteria, H. pylori constitutively releases outer membrane vesicles (OMVs) from the surface of the cell envelope both in vitro and in vivo. These 20-250 nm diameter, spherical, and bilayered vesicles are packed with outer membrane proteins (OMPs), peptidoglycan, and lipopolysaccharide(LPS). These vesicles represent an important means of H. pylori host-pathogen interactions as evidenced by their ability to deliver active virulence factors directly to gastric epithelial cells and modulate host immune responses. This study investigated H. pylori OMVs biogenesis from three aspects: the pathogenic molecules assembly, the influence of outer membrane (OM)homeostasis on OMVs formation, and LPS role in OMVs biogenesis.
As a characteristic virulence factor, the sorting signal of vacuolating cytotoxin (VacA) to H. pylori OMVs was investigated based on the 19 vacA gene mutations generated in this study.The results proved that only the VacA mature cytotoxin was released to the extracellular space and existed in both OMVs-associated and free-soluble forms. The study also found that only the oligomeric VacA could be sorted to H. pylori OMVs by attaching to the vesicles surface. Furthermore, the autotransporter character of VacA protein was also exploited for loading heterologous protein to OMVs, which demonstrated the potential for the development of H. Pylori OMVs based vaccines.
| Original language | English |
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| Qualification | Doctor of Philosophy |
| Supervisors/Advisors |
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| Publication status | Unpublished - 2015 |
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