Research carried out by Laetitia Van Wonterghem
The dissemination of antibiotic resistance mechanisms hampers the treatment of common infectious diseases. Especially transfer through conjugation is a major concern. Some plasmid-encoded conjugation factors have been studied with the view to inhibiting their products. However, these targets are specific to only one or a few conjugative elements. We aim to discover broadly conserved targets on which distinct conjugative elements rely. To this end, we focus on the identification and characterisation of chromosomally-encoded host factors involved in conjugation.
Overview of conjugation. Conjugation involves the physical connection of a donor (green) and recipient cell (yellow). Subsequently, the plasmid (black) is processed to single-stranded DNA and secreted from the donor to the recipient. The second strand is synthesized by rolling circle amplification in both donor and recipient cell. Conjugation involves plasmid-encoded factors as well as factors encoded on the chromosome (blue).
In collaboration with the University of Gothenburg, thousands of bacterial genotypes differing at a single known locus are being screened for their potency to exchange resistance factors by conjugation. In addition, de novo mutations promoting conjugation will be revealed using experimental evolution. Subsequently, the results will be extended to diverse conjugative elements. Moreover, a selection of strains will be analysed in full kinetic detail using time-lapse fluorescence microscopy.
Combined, our findings will result in a comprehensive understanding of host factors controlling conjugation, which in term might lead to novel approaches to halt the spread of antibiotic resistance.