Third Party Funds Group - Sub project
Start date : 01.01.2009
End date : 31.12.2012
Extension date: 30.06.2013
In frame of sub-project B5, interactions of pathogenic bacterium Corynebacterium diphtheriae with human host cells are investigated. In the previous funding period we could demonstrate that the DIP1281 protein is crucial for adhesion to the host and invasion into host cells. Furthermore, we were able to show that pili are - although important for host cell recognition and attachment - not exclusively determining adhesion rate. In fact, also a pilus-free strain investigated by us showed strong attachment to epithelial cells. High numbers of extended pili even seems to be counterproductive to invasion. While adhesion did not result in a signaling response by reporter host cell lines, we could show that the NFκB pathway is activated as a result of C. diphtheriae internalization. Based on the results obtained in the previous funding period, we will concentrate on the internalization process of the bacteria and the establishment of C. diphtheriae within the host in three different subprojects. In subproject 1 we will use a Caenorhabtitis elegans worm model established by us to characterize new virulence factors. In subproject 2, the survival of C. diphtheriae in macrophages will be investigated and compared to the behavior of related species Corynebacterium glutamicum, Corynebacterium pseudotuberculosis and Corynebacterium ulcerans using mainly a combination of molecular biology-based approaches and fluorescence microscopy. Subproject 3 will concentrate on bacterial effectors, which are (i) manipulating the internalization machinery of the cell and (ii) interact with signaling pathways of host cells.