The impact of Gene Transfer Agents on bacterial fitness and evolution

Infections with antibiotic resistant bacteria are an increasing threat to human
health and, if left unchecked, deaths per year are projected to rise substantially.
The primary mechanisms for rapid spread of antimicrobial resistance (AMR) and
virulence genes are known collectively as Horizontal Gene Transfer (HGT).
Traditionally, HGT consists of three mechanisms – conjugation, transformation
and transduction; however, a fourth mechanism - Gene Transfer Agents (GTAs),
has received little attention to date. GTAs are small viruses that transfer random
fragments of host bacterial DNA between cells. Unlike true viruses, whose
primary aim is self-preservation, GTAs have no preference for the spread of their
own genes. It is the lack of DNA selectivity that makes GTAs particularly
intriguing and means that the variety of genes that can be transferred by GTAs is
unlimited. Recently, an eye opening study in Science reported phenomenal
frequencies of antibiotic gene transfer by GTAs – often orders of magnitude
greater than more established mechanisms. GTAs are likely to be important
drivers of genome plasticity in the environment and may have a role in disease
evolution.
Despite the potential impact of GTAs, the direct benefits they provide to their
host to justify their conservation remain a mystery. This project will be
multidisciplinary, combining evolutionary microbiology, microbial genetics,
molecular biology and modelling. In particular, we will identify the genes and
pathways that provide a competitive advantage for GTA producers and dissect
the benefits they provide to their host. You will use techniques including
mutagenesis, cloning, fluorescence imaging, flow cytometry, next generation
sequencing, competition assays and bioinformatics. The department offers
opportunities for advanced training in use of cutting edge technologies and data
analysis. You will also be offered varied graduate skills training together with
valuable academic experience such as attendance at conferences and seminar
series plus opportunities to participate in outreach activities.