Project description
Mechanistic insight into bacterial meningitis
Bacterial meningitis is a serious infection that causes inflammation of the protective membranes covering the brain and spinal cord. It is caused by bacteria such as Neisseria meningitidis and exhibits high mortality rates despite antibiotic treatment. Funded by the European Research Council, the DESTOP project is working under the hypothesis that vascular colonisation by bacteria leads to antibiotic resistance. Researchers will decipher meningitis pathogenesis mechanisms by investigating the processes of bacterial adhesion and membrane deformation, and intravascular coagulation caused by bacteria. Apart from fundamental insight, the work has the potential to lead to novel strategies implicating vascular colonisation for enhancing meningitis treatment.
Objective
Before the antibiotic era chances of survival to bacterial meningitis were minimal. Nevertheless, nearly 100 years later, surprisingly little progress has been made and mortality rates currently remain unacceptably high (10-25%). Supported by clinical and experimental data, the central concept of the Destop project is that bacteria rapidly become insensitive to antibiotics during infection, which leads to treatment failure. We hypothesize that the emergence of such antibiotic insensitivity results from vascular colonization by Neisseria meningitidis i.e. when the bacteria adhere to the surface of the endothelium, proliferate and progressively occlude the vessel lumen. We propose to explore the mechanisms underlying four steps of vascular colonization that potentially alter bacterial sensitivity to antibiotics: (i) bacterial adhesion to the endothelium and auto-aggregation; (ii) colonization dependent changes in bacterial physiology, (iii) bacteria-induced plasma membrane deformation shielding adhering bacteria, and (iv) bacteria-triggered intravascular coagulation. For this, we will develop a multidisciplinary approach that involves: an in vivo humanized mouse model and innovative microfluidic devices - vessel-on-a-chip model and a bacterial confinement chamber. The Destop project will not only provide novel mechanistic insights in the meningitis pathogenesis process and allow to develop novel strategies to combat bacterial meningitis but also have broader impact by providing a better understanding of how tissues, as a context for infections, reduce the efficiency of treatment of numerous other bacterial pathogens.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine physiology
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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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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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.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75654 PARIS
France
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