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 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 three sections:

1) The model GTA is found in the α-proteobacterium Rhodobacter capsulatus and homologous GTAs are well conserved throughout the Class. Given that R. capsulatus GTAs do not mobilise their own genes and GTA release leads to host cell lysis, it is unclear how they justify their conservation. This project will use competition assays to determine the evolutionary advantage of GTAs when the host is faced with different biotic and abiotic stresses.

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.

A representative sample of the putative GTAs identified above will be selected for further study to determine the rates of gene transfer they are capable of and to assess their potential impact on the spread of virulence genes. Evolutionary experiments will be used to evaluate the impact of these GTAs on their host bacteria under natural conditions and stresses.