The Evolution of Horizontal Gene Transfer in Microbial Communities

Horizontal gene transfer (HGT) refers to a group of processes by which genetic information moves between individuals, in contrast to movement via sexual reproduction or clonal inheritance. These processes include transposition within genomes, and movement between individuals of the same and different species (transformation, transduction and conjugation). Because microbes reproduce asexually, HGT is the microbial mechanism of recombination, a fundamental process for enhancing adaptation. Thus, understanding HGT is vitally important in understanding microbial evolution, and the evolutionary origins of life.

Furthermore, HGT is of contemporary interest due to its role in the transmission of antimicrobial resistance (AMR) across species boundaries. While the discovery of antibiotics has been invaluable, their use provokes an increase in prevalence of existing resistance genes, and the evolution of new resistance where none previously existed. Human medical and agricultural use of antibiotics has been excessive in many parts of the world, and has rendered many antibiotics ineffective within a few years of use. We are now in a situation where effective antibiotics are few, and the development of new antibiotics is a slow process, with little financial incentive. Unless a solution is found, some estimates alarmingly state that we could see a return to the middle ages, where common illnesses are untreatable.

Conjugation is particularly relevant to the rise of AMR due to the autonomous replication and transmission of plasmids, and their ability to carry whole cassettes of genes, which are known to include resistance to multiple antibiotics. Thus, the study of conjugation is of primary importance to tackle the rise of AMR. Progress has been made in understanding the biochemistry of conjugation, plasmids, and the genes they carry. In addition, plasmid-host dynamics have been studied using population biology models. Models can be used effectively to isolate and explore mechanistic elements of complex systems, and to run simulations, which enable greater understanding of how AMR could be tackled. However, these models tend to involve only one or two species, and do not accurately reflect the complexity of microbial communities.

In my Masters project, which I completed recently, I extended a single-species population biology model to explore plasmid-host dynamics in two species. I found complex and unexpected interactions, including oscillatory dynamics, and the potential for species' coexistence on a homogeneous media. Unfortunately, I found difficulty in obtaining reliable parameter estimates, which hindered the analysis, validation and interpretation of the model. While I have since found some experimental data in the literature, it is difficult to assess the distribution of the needed parameters, such that many conjugation models remain unvalidated by experimental data.

With this in mind, I have identified 3 areas for my PhD research:

1. Expand and extend the model I used in my Masters project to reflect the complexity found in microbial communities. This will include ecological interactions, multiple species and evolutionary capacity for the plasmid and hosts.

2. Perform microbial community experiments to validate and assess these community models.

3. Conduct a metaanalysis of published parameter data to measure the distribution of parameters and assess the breadth and coverage of data across bacterial phylogenies. This will aid accessibility of reasonable parameter estimates for use in models, and the evaluation of the effectiveness of strategies to combat AMR. In addition, these distributions will give an indication of the importance of conjugation as an adaptive recombinatory process.