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 the frame of a JPIAMR project on "Predicting cell-cell horizontal transmission of antibiotics resistance from genome and phenome (TransPred)", we have performed genome-wide association studies revealing a number of candidate genes that drive conjugation. In term, these genes could be exploited for the development of conjugation inhibitors that are expected to slow down the spread of antibiotic resistance.
Van Wonterghem L., De Chiara M., Liti G., Warringer J., Farewell A., Verstraeten N., Michiels J. (2022). Genome-wide association study reveals host factors affecting conjugation in Escherichia coli. Microorganisms, 10(3):608.