Project description
New strategies to combat tuberculosis with antibiotics
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant health threat due to its infectious nature, drug resistance, and the need for prolonged treatments. While beta-lactam antibiotics (BLAs) are commonly used for other bacterial infections, they have not been effective against TB due to Mtb's resistance mechanisms. With the support of the Marie Skłodowska-Curie Actions programme, the BAN-BOOT project aims to inhibit the enzyme beta-lactamase which is present in Mtb and responsible for the ineffectiveness of BLAs. The team will develop and test specific enzyme inhibitors to enhance drug penetration through the bacterium and reduce the Mtb load in patients.
Objective
Tuberculosis (TB) is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb), one of the most dangerous aerobic bacteria. The need for long-term treatments and the increase in drug resistance mechanisms make it necessary to urgently develop new strategies to combat this potentially lethal pathogen.
beta-Lactam Antibiotics (BLA) are the most widely used and safest antibiotics in the clinic and include several classes such as penicillins, cephalosporins and carbapenems. However, historically these agents have not been used to treat TB. There are two mechanisms of resistance to BLA in Mtb: the cell envelope rich in lipoglycans which acts as a barrier for the penetration of many drugs, including BLA, and the expression of BlaC, a specific beta-lactamase enzyme capable of hydrolyze and inactivate the BLA. Recent studies have shown that the combination of meropenem (a beta-lactam carbapenem), amoxicillin (a beta-lactam penicillin) and clavulanate (a beta-Lactamase inhibitor) markedly reduced the Mtb load in the patients sputum after two weeks, therefore giving new hope to the use of BLA to tackle the tuberculosis epidemic.
This proposal aims to develop new compounds that behave as BLA adjuvant for anti-Mtb treatment with a dual mechanism of action. We will design and synthesize novel Boronic Acid Transition State Inhibitors (BATSIs) as inhibitors of BlaC, the beta-lactamase expressed in Mtb, and investigate whether they can be derivatized to become disrupting agents of Mtbs unique outer capsule made of lipoglycans, to promote better penetration of drugs into the cell. This project will also investigate the possibility of improving the penetration of molecules into the necrotic granuloma formed in vivo as part of the disease process, by developing a lipid-based prodrug strategy.
To achieve these specific objectives, the project will be divided into three main work packages, involving a combination of biological, chemical, and analytical expertise.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences clinical medicine pneumology tuberculosis
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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.
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
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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2023-PF-01
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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.
41121 Modena
Italy
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.