Grant: Team Grant: Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)

Antimicrobial resistance (AMR) spreads at an alarming pace resulting in continuous emergence of more virulent pathogens and multidrug-resistant 'superbugs'. Mobile genetic elements (MGE) provide a major mechanism to transfer AMR genes in hotspots of microbial interaction, including the bacterial communities in the human gut. However, the dynamics and mechanisms of movement of such 'jumping genes' are poorly understood. It is unclear how often they move, which natural and man-made compounds influence their movement, and how their movement occurs at the molecular level. Here we aim (i) to annotate and characterize MGEs in diverse bacterial genomes and metagenomes in order to characterize their genetic cargos and dynamics of transfer; (ii) to study the impact of antibiotic treatment on MGE-mediated gene transfer in patients; (iii) to analyse the influence of microbial compounds and human drugs on AMR transmission; and (iv) to dissect the structure and functioning of the molecular machines involved. Our work will shed light on AMR transfer at all scales from atomic resolution through bacterial and animal models to ecosystems in human patients and at the population level. To achieve these ambitious aims, our multidisciplinary consortium brings together leading scientists with complementary expertise in metagenomics, infection biology, medicine, molecular genetics, chemical biology, and structural biology. We will provide long-sought insights into the mechanisms of AMR dissemination, opening doors to novel intervention strategies aimed at reducing active transfer of AMR genes.