- To determine how Listeria cross the intestinal barrier. - To know how Listeria breach the endothelial barriers. - To characterise at molecular, cellular and pathophysiological level how Listeria interact with target organs.
- To identify listerial molecular determinants involved in tissue and cell tropism and the corresponding mammalian cell receptors.
- To develop in vivo and in vitro models useful in studying specific aspects of the pathogenesis of Listeria infection, with possible applications for research on other micro-organisms .
Listeria monocytogenes is a facultative intracellular pathogen. It is the etiologic agent of listeriosis, an emerging foodborne infection of increasing public health concern and with a great economic impact on food industry in Europe. Listeriosis is one of the most lethal bacterial diseases; clinical manifestations include meningitis and/or encephalitis, abortion as well as infection of the new-born and septicemias. The infection is opportunistic and affects predominantly pregnant women, babies, elder persons, and immunocompromised people including AIDS patients. In addition, Listeria micro-organisms are relevant for biomedical research as they provide a model system for the molecular and cellular analysis of intracellular parasitism. For these reasons, few bacterial pathogens have attracted more attention than Listeria monocytogenes and, in last years, important advances in the understanding of the cell biology of Listeria infection have been attained, and a number of key listerial virulence determinants have been identified. However, the actual state of knowledge provides only a very partial view on how Listeria interact with the infected host and there are still many important, open questions that need to be investigated. In this project, a core of scientists currently working on Listeria pathogenesis in Europe will work co-ordinately to elucidate several unknown aspects that are relevant for the understanding of Listeria pathogenesis. Issues that will be addressed include: mechanisms used by pathogenic Listeria for crossing the intestinal barrier and translocating to primary target organs; mechanisms involved in adherence, invasion and crossing of endothelia; pathophysiology of Listeria infection in target organs (liver, brain and placenta); genetic and molecular determinants of Listeria virulence involved in tissue and cell tropism and the corresponding mammalian cell receptors; and signal transduction pathways and effector molecules involved in the interaction of Listeria with the target cells. Experimental approaches will include in vivo animal models and histopathological analyses, in vitro cell culture models, and techniques of cell biology and bacterial genetics.
Funding SchemeCSC - Cost-sharing contracts