Virulence mechanisms of pathogenic Yersinia: aspects of type III secretion and twin arginine translocation
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
The pathogenic bacteria Yersinia pestis and Y. pseudotuberculosis are related to the degree where the former is considered a subspecies of the latter, and still they cause disease of little resemblance in humans. Y. pestis is the causative agent of lethal bubonic and pneumonic plague, while Y. pseudotuberculosis manifests itself as mild gastroenteritis. An important virulence determinant for these species is their ability to secrete and inject toxins (Yop effectors) into immune cells of the infected host, in a bacterium-cell contact dependent manner. This ability depends on the extensively studied type III secretion system, a highly complex multicomponent structure resembling a needle. The induction of Yop secretion is a strictly controlled event. The two structural type III secretion components YscU and YscP are here shown to play a crucial role in this process, which is suggested to require an YscP mediated conformational change of the C-terminus of YscU. Proteolytic cleavage of YscU within this domain is further revealed to be a prerequisite for functional Yop secretion. The needle subcomponent itself, YscF, is recognised as a regulatory element that controls the induction of Yop effectors and their polarised delivery into target cells. Potentially, the needle might act as a sensor that transmits the inducing signal (i.e. target cell contact) to activate the type III secretion system. Secondly a, for Yersinia, previously unexplored system, the Twin arginine translocation (Tat) pathway, is shown to be functional and absolutely required for virulence of Y. pseudotuberculosis. A range of putative Yersinia Tat substrates were predicted in silico, which together with the Tat system itself may be interesting targets for future development of antimicrobial treatments.
Place, publisher, year, edition, pages
Umeå: Molekylärbiologi (Teknisk-naturvetenskaplig fakultet) , 2005. , 67 p.
Molecular biology, Yersinia pestis, Yersinia pseudotuberculosis, bacterial pathogenesis, type III secretion, twin arginine translocation, virulence mechanisms, YscU, YscP, YscF
Biochemistry and Molecular Biology
Research subject Molecular Biology
IdentifiersURN: urn:nbn:se:umu:diva-619ISBN: 91-7305-948-XOAI: oai:DiVA.org:umu-619DiVA: diva2:144012
2005-11-25, Lecture Hall "Major Groove", 6L, NUS, Umeå Universitet, 901 87 Umeå, 10:00
Salmond, George, Professor
Forsberg, Åke, Professor
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