Objective
The rapid and ongoing resistance to all commonly used antibiotics by pathogenic bacteria urgently requires the development of a novel class of antibacterial drugs. This can be achieved by targeting essential processes in the cell. In this Project we propose to develop different strategies to target and inactivate the replicative DNA helicases, that are required in an essential process: the copy of the genetic material during the bacterial cell cycle. The inactivation of replicative DNA helicases is lethal to bacteria. The new knowledge of the structure of replicative DNA helicases and the proteins that interact with them will make possible the design of compounds that will target the helicases. The novelty of this approach is to target replicative DNA helicases which are not inhibited by currently available antibiotics.
The main effort of this project will be directed toward the analysis of the replicative helicases, their carriers and helicase inhibitors of Gram-negative (E. coli) and Grampositive (B. subtilis ) bacteria. Three converging strategies, explored by a multi-disciplinary team, will be used. First, the characterization of replicative DNA helicases and of known antihelicase proteins, paying special attention to the protein interfaces involved in the helicase-antihelicase interaction. Second, the search for and characterization of natural products and as well as newly designed ones able to inhibit the activity of replicative helicases in-vitro. Finally, we will develop in vivo screening methods to examine the efficiency of these compounds as antibiotics.
In summary, this project involves the functional and structural analysis of replicative DNA helicases and helicase-inhibitors, and the design of antimicrobial agents with antihelicase activity. The participation as a full partner of a Pharmaceutical Industry, Glaxo Wellcome, a leader in the field of new antimicrobials, guaranties the effective utilization and exploitation of the results obtained in this project.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
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Topic(s)
Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
MADRID
Spain