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 natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistancenatural sciencesbiological sciencesmicrobiology Keywords nitric oxide nitrosative stress target validation truncated hemoglobin Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Topic(s) HEALTH-2007-2.3.2-12 - Highly innovative research in HIV/AIDS, malaria and tuberculosis between Indian and European partners Call for proposal FP7-HEALTH-2007-B See other projects for this call Funding Scheme 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 See on map Region Este Cataluña Barcelona Activity type Higher or Secondary Education Establishments Administrative Contact F. Javier Luque (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH India EU contribution € 54 000,00 Address Anusandhan Bhawan, Rafi Marg 2 110001 New Dehli See on map Activity type Research Organisations Administrative Contact Kanak Dikshit (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSIDAD DE BUENOS AIRES Argentina EU contribution € 125 750,00 Address CALLE VIAMONTE 430 1053 Buenos Aires See on map Activity type Higher or Secondary Education Establishments Administrative Contact Dario Ariel Estrin (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS Spain EU contribution € 285 216,00 Address CALLE SERRANO 117 28006 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Administrative Contact Mar Sainz Ferrer (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data THE UNIVERSITY OF SHEFFIELD United Kingdom EU contribution € 404 500,00 Address FIRTH COURT WESTERN BANK S10 2TN Sheffield See on map Region Yorkshire and the Humber South Yorkshire Sheffield Activity type Higher or Secondary Education Establishments Administrative Contact Ben Williams (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
