Molecular mechanisms required for injection of Yersinia outer proteins (Yops) into host cells, and consequences for the host immune response

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Many pathogenic bacteria express type three secretion systems (TTSS) by which they inject toxins into host cells in order to evade defense mechanisms of the host. An important virulence mechanism of pathogenic Yersinia enterocolitica is to inject by a TTSS Yersinia outer proteins (Yops) into host cells. A -lactamase reporter system for tracking Yop injection allowed us to gain new insights into Yop injection by Y. enterocolitica. By means of the experiments described in this proposal we want to pursue these studies in order to elucidate (i) how host cell 1 integrins and 1 integrin-mediated signalling events upon interaction with Y. enterocolitica (particularly invasin protein and Yersinia adhesin A) facilitate Yop injection into different host cell types, and (ii) how host cells (dendritic cells, B and T cells) that are injected by Yops in experimental mouse infection in vivo are actually affected in their immunological functions. This will be accomplished by means of Y. enterocolitica mutant strains including a -lactamase reporter system, and infection of cell lines as well as mice with mutated 1 integrins. The results of these investigations will increase the understanding on how TTSS act in bacterial infections and might provide a molecular basis for novel therapeutic strategies to inhibit TTSS or to take advantage of TTSS as delivery systems for vaccines or therapeutics.