Title:

Investigating fosfomycin resistance patterns in Shigella sonnei

Summary:

Shigella spp. is an important diarrhoeal pathogen and S. sonnei is the most prevalent pathogen in high income countries including the UK. Shigella spp. are also recognised by the WHO as an AMR priority pathogen for which research is urgently needed. Following the international rise of extensively drug resistant S. sonnei, fosfomycin has recently been recommended as frontline therapy in the UK, but little is known about the distribution of fosfomycin resistance owing to the lack of routine testing. In this project, we will utilise a representative collection of ~200 clinical samples collected by the UKHSA (coupled with genome sequences from routine surveillance) to understand the prevalence, phylogenetic distribution and mechanisms of fosfomycin resistance in S. sonnei through AMR gene screening, phenotypic testing and Genome Wide Association Study.

The specific objectives of this project are to:

· Determine the population structure of the isolate collection.

· Determine the resistance phenotype and genotype distribution for fosfomycin in the isolate collection.

· Incorporate the findings into the phylogenetic tree and use that in GWAS to identify genetic markers associated with fosfomycin resistance in S. sonnei.

Required knowledge:

• Basic wet laboratory skills and an understanding of aseptic technique.
• Any previous knowledge in phylogenetic tree construction/GWAS will be advantageous but not required.

Supervisors:

Day-to-day supervisor: P. Malaka De Silva (pm823@cam.ac.uk)

Co-supervisor: Kate S. Baker (kb827@cam.ac.uk)

Department of Genetics