Identification of determinants of horizontal transmission of resistance factors
The overall aim is to identify bacterial and plasmid determinants for effective horizontal gene transfer with a long term aim of restricting antibiotic resistance by chemical inhibition of horizontal gene transfer.
Project supported by CARe (2,14 MSEK) 2016
PI: Anne Farewell
Collaborators: Jonas Warringer, Per Sunnerhagen, Ed Moore, Joakim Larsson Malte Hermansson and Carl-Fredrik Flach
We will set-up a massive scale experimental evolution assay that captures the rates of transfer of antibiotic resistance factors between bacteria. Antibiotic resistance development associated with horizontal transfer of resistance factors will be followed in real time. Using the E. coli as genetic model, we will uncover what host cellular features that are required for transmission and horizontal spread of resistance by screening a complete collection of deletion strains, as well as a unique collection of clinical isolates. We will further establish what genetic features in plasmid backbones that stimulate the horizontal spread of antibiotics resistance by screening a collection of plasmids (or other conjugative elements) isolated from antibiotic resistant strains isolated downstream of antibiotic production plants. In a follow-up project, genetic factors required for rapid horizontal transmission of antibiotic resistance will be passed to the synthetic chemist and structural biology groups as candidates for the development of chemical inhibitors. The ultimate aim is to identify drugs which can be used to slow down antibiotic resistance development for use in combination therapy aimed at decreasing the spread of resistance within as well as between patients.