Characterization of type III secretion system-dependent protein secretion in Y. enterocolitica

The type III secretion system (T3SS) is utilized by many Gram-negative bacteria to promote survival in a variety of symbiotic or pathogenic relationships. Many pathogenic bacteria use their T3SS, commonly called the injectisome, to translocate bacterial effector proteins to manipulate host cells and...

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1. Verfasser: Milne-Davies, Bailey Abigail
Beteiligte: Søgaard-Andersen, Lotte (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2021
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Zusammenfassung:The type III secretion system (T3SS) is utilized by many Gram-negative bacteria to promote survival in a variety of symbiotic or pathogenic relationships. Many pathogenic bacteria use their T3SS, commonly called the injectisome, to translocate bacterial effector proteins to manipulate host cells and promote infection. The injectisome consists of a membrane-spanning nanosyringe that translocates effector proteins from the bacterial cytosol into the host cytoplasm. Using Yersinia enterocolitica as a model organism, we characterized the post-secretion events (deactivation, reactivation, and re-initiation of division following secretion) and explored secretion regulation prior to and during activation. Our results show that Y. enterocolitica can quickly adapt to different environmental conditions, allowing rapid deactivation of secretion and when re-introduced into a secreting environment, the bacteria immediately reactivate the T3SS. Notably, Y. enterocolitica survives secretion and can reestablish growth and division. We also established cell culture-based infection assays to test controlled protein translocation by the T3SS and demonstrated that the cognate chaperone is vital for exporting complex non-native proteins into host cells. The effector chaperones don’t appear to directly interact with the injectisome, but are essential in establishing efficient effector export. Furthermore, we show that Yersinia appears to prepare a small pool of pre-synthesized effectors that is ready to be exported once secretion is activated. Lastly, we found that the gatekeepers, which controls the activation or inhibition of effector secretion, are localized throughout the cytosol, suggesting Y. enterocolitica utilizes a different mechanism to govern secretion than E. coli. The data shows that events during and after secretion are highly regulated, utilizing a variety of mechanisms to sense and adapt to the environment and promote swift and decisive secretion to bolster survival during infection.
Umfang:137 Seiten
DOI:10.17192/z2021.0101