Unravelling the genetic basis of phage-antibiotic synergy with Ralstonia solanacearum plant pathogen

Supervisor:  Dr Ville Friman

Co-Supervisor:  Dr Daniel Jeffares

Project description:

Plant pathogenic bacteria cause considerable economic losses globally due to damage to crops. As various agrochemicals are becoming ineffective due to rapid resistance evolution new control methods are urgently required. One alternative method is microbe-based biocontrol: the use of natural soil microbes, such as parasitic viruses (phages) and antimicrobials-producing bacteria, to control the pathogen.

A growing body of evidence suggests that combinations of phages and antimicrobials are more effective at killing a greater fraction of the pathogenic bacteria than if the agents were applied independently. This phenomenon is called Phage-Antibiotic Synergy (PAS). While PAS can be explained by evolutionary ‘trade-offs’, where bacterial adaptation against phages leaves them more susceptible to antibiotics, the genetic basis of PAS is still poorly understood.

The PhD project will concentrate on studying the underlying genetics of PAS in the biocontrol of Ralstonia solanacearum, a plant pathogenic bacterium capable of infecting more than 200 plant species including many economically important crops. The Friman lab has demonstrated that Ralstonia infections of tomato can be suppressed effectively by using a combination of bacteriophage and bacteria that produces an antibiotic (Bacillus amyloliquefaciens)1. In this project, this complex dynamic process will be described at molecular detail by sequencing. This is also expected to reveal potentially important genetic changes for bacterial pathogenesis. For example, it has been found that phage selection can affect the pathogen virulence2, which could indirectly affect the severity of disease outbreaks.

In order to study these questions, the student will use experimental evolution approach to evolve full genome sequenced R. solanacearum K-60 strain in the presence of different phage and B. amyloliquefaciens strains and characterize changes in pathogen resistance evolution at both phenotypic and genomic level. The aims of the project are:

1. To compare phage-antibiotic synergy between different phage and B. amyloliquefaciens strain combinations
2. To unravel the genetic basis of phage-antibiotic synergy using dynamic population sequencing and state-of-the-art bioinformatics
3. To understand the role of genome-wide and population-wide changes during biocontrol, including correlated changes in pathogen virulence, metabolism and colonization

The proposed research combines laboratory-based direct experimentation, next generation genome sequencing, bioinformatics and evolutionary biology to understand the biocontrol of economically important plant pathogen in an agricultural context. Unravelling the genetic basis of PAS is important for the further development of novel biocontrol strategies and phage and bacteria-based therapies in the medical context.

We strongly encourage you to email the project supervisor prior to submitting an application to discuss your suitability for this project.  Please email: ville.friman@york.ac.uk

Funding:  This studentship is fully funded for 3 years by the Department of Biology and covers: (i) a tax-free stipend at the standard Research Council rate (£14,533 for 2017-2018, to be confirmed for 2018-2019), (ii) research costs, and (iii) tuition fees at the UK/EU rate.

Start date: October 2018

Please read the 'How to apply' tab before submitting your application.

CLOSING DATE FOR APPLICATIONS: 23h59min on Sunday 7 January 2018

Interviews will be held on Monday 5 or Tuesday 6 February 2018 - TBC