Research
We study the interactions between bacteria and their mobile genetic elements (MGEs). Promoting successful transmission of MGEs within bacterial communities can benefit us in several contexts, from phage therapy to biotechnological applications. On the other hand, MGEs frequently confer antimicrobial resistance (AMR) and virulence traits to pathogens, making the control of their transmission of great interest for public health.
The spread of AMR is for a large part due to the carriage of AMR genes on conjugative plasmids, genetic elements that can spread horizontally by conjugation. Conjugative plasmids have allowed key AMR genes to spread across pathogenic species and become a world-wide problem;at shorter time-scales, plasmid conjugation has been implicated in pathogen epidemics and single patient infections in hospital settings. To limit AMR spread, it is thus key to understand what factors shape the conjugative transmission of AMR plasmids.
Eco-evolutionary drivers of plasmid transmission
We are interested in the environmental and selective factors that shape the ecology and evolution of plasmid horizontal transmission. Recently, we showed experimentally that plasmids can rapidly evolve increased rates of horizontal transmission when they encounter frequent opportunities for transmission. The same experiment revealed that increased transmission can evolve via changes in plasmid copy number, leading to a coupling between selection for horizontal transmission and selection for high levels of AMR. We are now asking how general these results are across conjugative plasmids, and exploring the effect of other factors on the evolution of transmission.
Previously, Tatiana explored the social evolution of horizontal gene transfer during her PhD, using a synthetic experimental system as well as modelling. She demonstrated experimentally that horizontal transmission can promote cooperative behaviours, and developed new theory and experiments showing that bacterial hosts investing in plasmid transmission are themselves performing a cooperative behaviour.
Relevant papers:
From Tatiana’s PhD: Dimitriu et al PNAS 2014, PLoS Biol 2016, bioRxiv 2018;
Dimitriu, Microbiology 2022 (review)
Bacterial defence systems and plasmid transmission
To defend themselves against their parasites, bacteria carry a wide range of defence systems including restriction-modification systems and CRISPR-Cas systems. Defence systems are mostly studied as a defence against phages, viruses which cause bacterial death, but they can also act on conjugative plasmids. However, there is little data on how defence systems act against plasmid conjugation. We have begun exploring this focusing on the most prevalent bacterial defence systems, restriction-modification systems and CRISPR-Cas.
Relevant papers:
Dimitriu et al, Proc Roy Soc B 2019;
Dimitriu et al, Curr Biol 2020 (review);
Pursey, Dimitriu et al, Phil Trans Roy Soc 2022;
Dimitriu et al, Nucl Acids Res 2024.
Effect of antibiotic treatments on transmission and defences
We and others have observed that antibiotics can have multiple effects on factors influencing AMR spread: direct selection, but also indirect effects on plasmid conjugation, its evolution, and bacterial defence against MGEs. We will explore how these effects ultimately shape the spread of AMR.
Relevant papers:
Dimitriu et al, Cell Host Microbe 2022;
Pons, Dimitriu et al, PNAS 2023