Microbe-induced antimicrobial responses in host cells -subverting effects of microbial virulence effectors

Project description

Yersinia pseudotuberculosis is used as a model pathogen to study molecular mechanisms behind bacterial infection, with focus on the affected target cell. We study effects of virulence effectors, particularly YopH, identify targets that are investigated with regard to mechanisms and importance for antimicrobial effects.

Yersinia injects YopH into host cells. YopH causes resistance to phagocytosis by destroying integrin-connected focal complexes (dephosphorylating Cas and Fyb). Targeting of YopH to focal complexes, and to Cas/Fyb is essential for Yersinia virulence in mice. We have also found that Cas is critical for initial membrane protrusions and that certain signalling proteins, such as Rac, Src, and WASP participate in phagocytosis.

The methodology used is cell and molecular biology based and combined with advanced microscopy. To elucidate the role of the immune cell specific protein Fyb, we have used the yeast-two-hybrid system and identified a novel interaction partner with potential to modulate F-actin dynamics, mAbp1. The importance of this interaction will be investigated, and also other potential functions of Fyb. A proteomic approach is undertaken to find novel players in the phagocytic process. With 2-D DIGE we have found proteins that are differentially displayed in membrane fractions from non-infected and infected macrophages. These will be identified and investigated further. Another part of the project deals with effects of Yersinia on neutrophil function.