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Content archived on 2024-06-18

Unraveling the molecular mechanism of nitrosative stress resistance in tuberculosis

Objective

Tuberculosis is today amongst the major worldwide health threats. Treatment failure is unfortunately becoming more usual, especially in countries lacking the long and costly treatment adapted to patients. Thus, tuberculosis causes 2 million deaths every year and latently persists in over 1 billion individuals worldwide. Current treatments are challenged by multidrug resistant strains, drug side effects, and co-infections. Therefore, identification of potent, safety antimycobacterial agents is mandatory. However, the success of this strategy is largely determined by the detailed knowledge of their mechanism of action, which in turn depends on the validation of suitable biological targets. This project pursues the definition of new, complementary therapeutic approaches by identifying the molecular basis of the nitrosative stress resistance of M. tuberculosis. Our working hypothesis is that a decrease in the NO resistance of the microorganism should reduce significantly the capability to rest in latency, thus contributing to increase the efficacy of the therapeutic treatment. In this context, understanding of the NO detoxification activity played by M. tuberculosis trHbN is essential. Accordingly, our objectives are i) to unravel the molecular mechanism underlying the NO dioxygenase activity of M. tuberculosis trHbN, ii) to establish the structure-function relationships in trHbN and trHbO from M. tuberculosis, and iii) to identify the reductase protein system that helps trHbN to restore the ferrous state required to initiate the NO detoxification cycle. The outcome of the project should provide a firm basis to assess the viability of trHbN as a therapeutic target, and set up the background to exploit this knowledge in the design of innovative therapeutic strategies to fight the disease.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Call for proposal

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FP7-HEALTH-2007-B
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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.

CP-SICA - Collaborative project for specific cooperation actions dedicated to international cooperation partner countries (SICA)

Coordinator

UNIVERSITAT DE BARCELONA
EU contribution
€ 293 798,00
Address
GRAN VIA DE LES CORTS CATALANES 585
08007 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

No data

Participants (4)

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