Informing genomic surveillance by uncovering, phenotyping and prioritising resistance genes to new antibiotics
( NewResGenes )

Understanding the genetic and phenotypic diversity of antimicrobial resistance genes (ARGs) in One Health settings, throughout the environment, agriculture and clinics, is crucial for genomics-based surveillance of antimicrobial resistance (AMR). While much knowledge is being gained on the spread of known clinical ARGs, there is still a lack of systematic approaches to identify the resistance phenotypes of novel ARGs and how they disseminate into populations of pathogens. This major knowledge gap – especially substantial in the case of new antibiotics which are currently in clinical development – precludes our ability to detect and slow down the emergence of resistance. Here, we develop novel methods to discover, characterise and prioritise ARGs using a One Health approach to support genomic surveillance efforts world-wide. Specifically, we will systematically identify thousands of ARGs against multiple classes of novel and already widely used antibiotics in a diverse set of One Health settings using a combination of functional metagenomic screens, high-throughput gene synthesis, and genome-wide association studies. We will then experimentally characterise such ARGs in three of the most critical Gram-negative pathogens and rank them based on their risk of resistance dissemination using novel bioinformatics methods. This proof-of-concept study will provide integrated genomic and phenotypic reference data on ARGs against novel antibiotics and give the biomedical community guidelines on how to track and diminish the emergence of resistance.