Antimicrobial resistance (AMR) is a major challenge to human health, and infections due to resistant bacteria are predicted to exceed cancer as the primary cause of human mortality by 2050, and negatively impacting on world economy and social stability.

Photo of lab. work

Introduction, objectives and overview of the research programme

Prudent use of antimicrobials can slow down the development of AMR, but it cannot solve the challenges caused by multi-drug resistant bacteria (MDR), some of which are resistant to all of the current antimicrobials on the market. This requires novel antimicrobials, or drugs that can re-sensitize MDR bacteria to the existing antimicrobials. In accordance with this, the first priority topic in the Strategic Research and Innovation agenda of the Joint Programming Initiative on Antimicrobial Resistance[5], where Europe together with partner-countries coordinates research to solve the AMR crises, is discovery of new antimicrobials and therapeutic alternatives, and the improvement of current antibiotics and treatment regimens.

So far, metabolic enzymes have largely been ignored as targets for antimicrobials, and among the current antimicrobials, only sulfonamides target metabolic pathways. This is due to three knowledge gaps:

  1. We do not know how pathogenic bacteria modulate metabolic processes during infections, and hence prediction of essential reactions is difficult.
  2. Metabolic pathways often show redundancy, i.e. more than one pathway can lead to fulfillment of the same end-results, and currently we cannot predict which metabolic enzymes form relevant redundant pairs, and we lack screening approaches to find drugs that can target two redundant enzymes at the same time.
  3. We lack knowledge on which metabolic enzymes targets we should avoid due to toxicity caused by overlap in metabolic functions between eukaryotic and prokaryotic cells and good methods to predict this.

Due to recent technological advances within omics-technologies, computer modeling and drug screening platforms, we are now in a position, where these knowledge gaps can be closed, thereby significantly increasing the number of putative targets for antimicrobials. INNOTARGET will do this, and combined with state-of-the-art doctoral training, INNOTARGETS also provides research leaders for the future to both industry and academia.

The aim of INNOTARGETS is to train a new generation of early stage researchers (ESRs) in highly innovative approaches to identify metabolic drug targets in pathogenic bacteria. The proposed ETN closes fundamental gaps in European training. We will (i) educate young researchers in approaches to study bacterial metabolism during infection and use of this knowledge in antimicrobial target identification, a critical step to overcoming AMR, and (ii) offer them solid interdisciplinary training in infection microbiology, mathematical modeling and antimicrobial screening techniques. INNOTARGETS’ training equips our ESRs with a holistic view from bench-to-bedside and a creative mind-set with special attention to future clinical/industrial applications of newly developed technologies. This ambitious training program is only possible thanks to a unique consortium with worldwide experts from academic and industrial sectors from six countries, ensuring leading positioning in both the scientific aspects of AMR and target identification, and the inter-sectorial technology transfer onto applications and commercial products and services.

In summary, INNOTARGETS’ mission is to train our ESRs to become the first breed of dedicated experts within antimicrobial discovery with a unique and wide-reaching competence profile, including technical, interpersonal and complementary skill capable of working and collaborating along the continuous spectrum from basic biology to antimicrobial development and across academic and industrial environments. This training will significantly contribute to their employability as the future leaders in the field.