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Title [sv]
Typ VI sekretion hos Francisella tularensis - identifiering av de enskilda komponenternas funktion och deras betydelse för bakteriens virulens
Title [en]
A type VI secretion system of Francisella tularensis - defining the functions of its components and their contribution to virulence
Abstract [sv]
There are at least six specialized secretion systems in gram-negative bacteria. The Type VI secretion systems (T6SSs), identified in almost 100 different bacterial species, are essential for virulence of many important human pathogens such as Vibrio cholera and Pseudomonas aeruginosa. Still, the understanding of T6SSs in general is very incomplete. Our work will delineate the functions of 20 proteins of a putative T6SS encoded by a pathogenicity island of Francisella tularensis and determine if and how they contribute to virulence. By generating translational fusions of T6SS components and various reporters, we will be able to determine whether they are secreted during infection. The importance of the subcellular localization for the function of T6SS proteins will also be determined. Recently, we identified and characterized an essential interaction between IglA and IglB using the yeast two-hybrid system and alanine scanning mutagenesis. To gain further insight into the function of the complex, its structure will be solved by X-ray crystallography and the molecular targets identified by three-hybrid assays, pulldowns and immunoprecipitation. The relevance of homologous IglAB complexes in other T6SSs will be investigated by targeted mutagenesis. Screening will be performed to identify small molecular inhibitors of the interaction. Our work will help to identify the molecular mechanisms of a poorly understood secretion system essential for virulence of many human pathogens.
Principal InvestigatorSjöstedt, Anders
Coordinating organisation
Umeå University
2010-01-01 - 2012-12-31
DiVA, id: project:911Project, id: 2009-05026_VR

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