Objective
Legionella pneumophila is the infectious agent of Legionnaires' disease, a serious pneumonic illness of humans. This bacterium represents a facultative intracellular parasite that invades and proliferates in many types of eukaryotic cells, including fresh water protozoans, human alveolar macrophages and epithelia. Numerous bacterial factors have been identified as crucial for intracellular infection, however for majority of these activities, their role in virulence is unclear and/or their eukaryotic substrate(s) are unknown. Recently one of the Russian applicants (Y.B.) of the collaborative project discovered for the first time and isolated from L. pneumophila a protein (Lpg1368) possessing glucosyltransferase activity, which modifies an ~50kDa eukaryotic protein substrate. Moreover, using translated amino acid sequence of lpg1368 gene as a template, other products with ~20% identity have been identified on the Legionella chromosome (Lpg2862 and Lpg1488). Importantly, all three proteins exhibited sequence similarity with the catalytic domains of clostridial glucosylating toxins.
Thus, the main objective of the current proposal includes elucidation of the role of these glucosylating enzymes in the host-pathogen interaction of L. pneumophila. For this purpose a panel of multidisciplinary approaches will be used, including those from microbiology, molecular biology, eukaryotic cell biology and pharmacology, to elucidate the properties and functions of the L. pneumophila proteins and their target(s).
Moreover, it is proposed to study the transport mechanism involved in the introduction of the bacterial enzyme into the target cells. The results obtained during the project will be of major importance both for basic biomedical science to disclose molecular mechanisms of pathogen-host interactions, as well as for applied science to generate a background for development of new methods of diagnosis, therapy and prophylaxis of legionellosis and possibly, by analogy, of other infectious diseases.
Fields of science (EuroSciVoc)
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Funding Scheme
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Coordinator
FREIBURG
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.