Grant: Operating Grant: 16th JPIAMR transnational call for research projects (2023)

The majority of current resistance problems encountered in clinical practice start with the mobilisation of antibiotic resistance genes (ARGs) from the environment into clinical pathogens. Therefore, the pace at which a novel antibiotic will face resistance largely depends on how widespread the ARGs are and how easily they can be mobilised into the target bacteria to compromise the effect of the antibiotic. However, when it comes to antibiotics that are new on the market, we have little prior knowledge on which ARGs are going to be active against them. Such ARGs are usually spotted by clinicians when they have already become widespread among clinical pathogens. Here we propose novel experimental and computational methods to functionally annotate ARGs at an unprecedented scale and estimate the mobilisation potential of the found ARGs into target pathogens before they have spread widely. As a proof of concept study, we are going to investigate a diverse set of One Health settings for the potential to provide ARGs against future antibiotics for human use - those that are currently in clinical development. Furthermore, to expand our knowledge of ARGs for existing antibiotics, we are going to carry out the same experiments with a set of antibiotics that has been applied for decades. The advanced features of the proposed pipeline will provide accurate assessments of the risks and possible routes of emerging resistance from an early phase. The ultimate goal is to inform world-wide genomic surveillance efforts on how to better track the emergence and spread of resistance.