Flavodoxin inhibitors to kill resistant bacteria

Therapeutics

Research Project: 2019-06-01 - 2023-05-31
Total sum awarded: €1 110 420

This transnational collaboration gathers the expertise and resources required to address lead improvement to the point of producing novel antibiotics ready for clinical trials, and to clarify the overall importance of flavodoxin as a novel drug target. The project has two goals: 1. To culminate the improvement of inhibitors of the flavodoxin from H. pylori, which have shown efficacy against reference and clinical strains (including a clarithromycin-resistant one) and in a mice model. 2. To determine the relevance of flavodoxin as a novel drug target to fight bacteria which pose problems associated to antimicrobial resistance.

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  • Javier Sancho, University of Zaragoza, Spain (Coordinator)
  • Eliette Touati, Institut Pasteur, France (Partner)
  • Ultrich E Schaible, Research Center Borstel, Germany (Partner)
  • Alain Bousquet-Melou, Ecole Nationale Vétérinaire de Toulouse, France (Partner)

Some bacteria and other microorganisms are pathogens responsible for human infectious diseases. Bacterial infections are commonly fought using antibiotics or, more generally, antimicrobials. the prolonged use (and misuse) of antimicrobials over time to fight human infections has allowed some bacteria to develop molecular mechanism that neutralize antimicrobials. Such bacteria are in practice antimicrobial resistant and constitute a serious global threat to human health. In the European Union, antimicrobial resistance is responsible for 33,000 deaths annually and the costs of medical care and productivity losses are estimated in 1.5 billion euros. The bacteria Helicobacter pylori (Hp) has been identified by the WHO as one of the pathogens for which it is urgent to find new antibacterial compounds, due to the high incidence of antibiotic-resistant strains along with the fact that half of the world's population suffers from gastric infections caused by Hp, and because Hp infection constitutes a risk factor for developing gastric cancer. The Spanish-Franco-German project Flavodoxin inhibitors to kill resistant bacteria (FLAV4AMR), has been conceived as a transnational collaboration that brings together all expertise and resources needed to develop new antimicrobial compounds that could enter clinical testing and renew our arsenal against Hp. These novel antimicrobials act by a mechanism different from those of existing broad-range antimicrobials and therefore may be specific against Hp. Moreover they may not damage the beneficial microbiota and thus be useful for a personalize treatment of infectious diseases. The project is led by Javier Sancho (Biochemistry Professor, and researcher at the University Institute for Research on Biocomputing and Physics of Complex Systems - BIFI). "Our ultimate goal is to develop new flavodoxin inhibitors having significant antimicrobial activity, both for Hp and for other pathogens that present significant problems because of their antibiotic resistance, and that can reach the market within a reasonable time, then, having a high impact on medicine,"

Call

2018 - Innovations against antibiotic-resistant bacteria: New targets, compounds and tools