Antimicrobial resistance is a global health emergency. Caused by multi-drug-resistant bacterial pathogens, it is making common infections more and more difficult to treat. Gram-negative bacteria (GNB), a major cause of infections in recent years, are resistant to almost all antibiotics, leaving no option for treatment at all. BREAKthrough is a Doctoral Network which aims to make these bacteria susceptible to today’s standard-of-care (SOS) antibiotics.

Prof. Ruben Martin Group’s, from the Institute of Chemical Research of Catalonia (ICIQ-CERCA), receives funding from this programme. BREAKthrough is coordinated by the Université Catholique de Louvain and will count on seven more European partners, including research centres, universities and companies as well as 4 associated partners. It has started in 2023 and will be running for four years.

Funded by the Horizon Europe’s Marie Skłodowska-Curie Actions (MSCA) programme, the objective of BREAKthrough is to sensitise GNB to these antibiotics by making their outer membrane (OM) permeable. To this end, researchers will develop inhibitors of three protein machineries that are responsible for OM maintenance.

To achieve these goals, a multi-disciplinary academic-industrial consortium has been made-up of organic chemists, computational chemists and specialists in high-throughput drug screening, zebrafish infection models, bacterial morphogenesis, and the molecular biology of the three targets.

The expected outcomes of the BREAKthrough DN include (i) the development of new chemical space rules for drugs that need to cross the OM, (ii) the discovery of new inhibitors that interfere with OM maintenance to overcome the insensitivity of Gram-negative pathogenic bacteria towards SOS antibiotics and (iii) providing 10 Doctoral Candidates with scientific, technical, business and transferable skills to become professional drug developers with a keen eye for the hurdles in the development of these drugs in an industrial context.

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The “BREAKthrough Doctoral Network” is funded by the European Union under Grant Agreement 101072632.