Collaborative Projects

JumpAR: A multi-scale approach to understanding the mechanisms of mobile DNA driven antimicrobial resistance transmission

Antimicrobial resistance (AMR) is one of the greatest current global health challenges. It spreads rapidly resulting in the emergence of more dangerous bacteria. Mobile genetic elements, segments of DNA that can move between bacterial cells, constitute a major route for resistance transfer in hotspots of microbial interaction. There is poor understanding of how often such ‘jumping genes’ move, which natural and man-made compounds influence their movement, and how their movement occurs at the molecular level. Here, within the framework of an international consortium, we aim to survey mobile genetic elements, identify their resistance gene cargos, and explore the dynamics of their transfer between different bacteria. By drawing on available genome and metagenome sequencing data, we will gain a global picture of the abundance and distribution of mobile genetic elements, their resistance gene cargos, and transmission potential. In addition, using clinical samples (assembled at our Swedish consortium partner), we will chart the effects of antibiotics and other human drugs on mobile genetic element-mediated resistance transmission. Moreover, we aim to obtain insights into the structure and functioning of the molecular machinery involved in AMR transmission. Using biochemical and structural biology approaches we will elucidate the organization and chemical action of the protein-DNA complexes involved in resistance gene mobilization; and we will scout unanticipated modulators of AMR transmission in unbiased high-throughput screens with common human drugs. Candidate transfer effectors will then be further validated by us in vitro and by other consortium members in vivo. Our collective results will vastly expand our knowledge on the molecular processes and dynamics involved in mobile genetic element-driven resistance dissemination, opening doors to the development of novel intervention strategies as well as risk assessment and preventive measures aimed at reducing active transfer of resistance.