The impact of gene transfer agents on bacterial evolution

Horizontal Gene Transfer (HGT) is a fundamental and powerful process for the exchange of genes between bacteria. HGT drives bacterial evolution, adaptation and spread into new ecological niches and is the primary means for rapid distribution of characteristics such as antibiotic resistance. Antibiotic resistant bacteria are responsible for over 50,000 deaths a year in the EU & US, and it is predicted that this number will continue to rise without new treatments and practices.

Many aspects of HGT in bacteria have been extremely well studied but one mechanism that has been neglected so far is Gene Transfer Agents (GTAs). GTAs are small virus-like particles that are able to mediate high frequency, indiscriminate transfer of any gene between bacteria. When the genes in question are antibiotic resistance, virulence or fitness genes, this poses a clear and serious threat to human health.

This research project will aim to determine the role GTAs play in bacterial evolution, and will be broadly split into two sections:

1) The model GTA is found in the α-proteobacterium Rhodobacter capsulatus and homologous GTAs are highly conserved throughout the α-proteobacteria. It is known that production of GTAs leads to death of the host cell and, unlike true viruses, GTAs do not actively spread their own genes to new hosts. Using gene knock-outs that affect GTA production/receipt and a variety of evolutionary biology techniques, this project will determine how GTAs provide a selective advantage to their host and what pressures or stresses influence their impact.

2) Bioinformatics survey of pathogenic species for putative GTA genes. Discriminating GTA genes from bacteriophage genes is a key hurdle for GTA research. However, clear examples of GTA genes are identifiable in plant and animal pathogens in the α-proteobacteria e.g. Bartonella sp. and Agrobacterium sp., and this will be the starting point for this project. As more GTA “genomes” are identified the more certain we can be about the characteristics of a genuine GTA and, therefore, the more accurate our predictions for new GTAs in more distant species will be. Putative GTAs identified above will be assessed to determine rates of gene transfer, impact on fitness and spread of virulence genes.

We strongly encourage you to email the project supervisor prior to submitting an application to discuss your suitability for this project. Please email: [Email Address Removed]