Figure 1. Schematic overview of the screen. A donor strain carrying a conjugative antibiotic resistance (ABR) plasmid is mated with a recipient strain. The donor strain is unable to grow and form colonies due to a chromosomal mutation (indicated in red). The recipient is unable to grow because of inhibitory concentrations of the antibiotic in the medium. It is only upon transfer of the plasmid and its resistance gene that the recipient can grow.
Host factors involved in conjugative gene transfer
The spread of antibiotic resistance poses a major threat to health-care, leading worldwide to increased morbidity and mortality. The drastic decline in clinical potency of most of our frontline antibiotics is predominantly due to horizontal transmission of antibiotic defence factors. However, there is a general lack of knowledge on host factors controlling horizontal gene transfer in bacteria.
The main goal of this project is therefore to understand chromosomally-encoded host factors that are needed for conjugative transfer and this in full dynamic detail.
In collaboration with the University of Gothenburg, thousands of microbial genotypes differing at a single known locus are being screened for their potency to exchange resistance factors by conjugative transfer.
This is achieved using a massively parallelized experimental platform that monitors the growth of thousands of individual strains simultaneously.
In addition, we are using experimental evolution set-ups to select for and identify de novo mutations capable of promoting horizontal transmission of antibiotic resistance. Results will be verified in full dynamic detail using fluorescence microscopy and validated in two in vivo model systems. Combined, our findings will result in a comprehensive understanding of host factors controlling horizontal gene transfer, which in term might lead to novel approaches to halt the spread of antibiotic resistance.
Copyright 2019 by BAMdesign @ All Rights Reserved