The early years focused on building whole genome sequencing and bioinformatics capacity, and targeting key hospital-associated infection pathogens, allowing the genomics Team to gain an understanding of the natural variation in the population structure of S. aureus and E. coli and how that relates to a patient’s illness.
This year the omics Team based in Glasgow and St Andrews Universities have worked on:
- Collecting and sequencing, 1,000 S. aureus bacteraemia isolates from the national Reference Laboratories archives and 500 E. coli bacteraemia isolates from Greater Glasgow and Clyde. This latter set has direct linkage with clinical information and laboratory data via the West Safe Haven. Sequence analysis has commenced on the S. aureus isolates; the E. coli data has just become available.
- Near Real Time Sequencing (nRTS) has helped clinically in a number of outbreaks, or pseudo-outbreaks. Dr Ben Parcell, a Consultant clinical microbiologist working at Ninewells Hospital, NHS Tayside has been extensively using the nRTS facility in his infection control role. One of the outbreaks that was been identified was a cryptic outbreak of borderline oxacillin-resistant S. aureus (BORSA). The WGS data was used to define the outbreak and help in its control. A PCR screening assay was developed from the WGS data to allow rapid screening of samples to identify strains belonging to the outbreak clone.
- The capacity and expertise that has been developed through nRTS facility has allowed collaboration on a range of project looking at transmission and spread of pathogens associated with healthcare facilities and disease, these include: characterization of the genetic basis of borderline oxacillin resistant S. aureus; genomic epidemiology of S. aureus bacteraemias (SABs) in people who inject drugs (PWIDS); genomic epidemiology of S. aureus in Atopic Dermatitis (AD). These projects have facilitated work between the St Andrews and Glasgow teams, and have generated data that has been complimentary to the SHAIPI generated data, such and the S. aureus bacteraemia isolates, and helped in the interpretation of the data. For example, in the in Atopic Dermatitis study the within host diversity of the S. aureus carriage population have been examined. This information has been valuable in investigating the BORSA outbreak.
- Work has started at looking at cost benefit analysis of utilising nRTS in the clinical environment, both in terms of time saved and unnecessary testing avoided.
- To complement the nRTS capacity that the Illumina MiSeq provides, a pipeline for the sequencing of clinical samples using the Oxford Nanopore MinION platform has been established at the University for St Andrews.
In particular, this long read technology has proved invaluable for producing high quality references sequenced for mapping MiSeq data to, and also for resolving mobile genetic elements, such as plasmids. This has been used for VRE, BORSAs, SABs, ECBs and Serratia marcescens.
- Collaboration with Uganda as part of DHSC and MRC Burden and resistance of AMR in low and middle income countries. Further funding has been obtained from the University of St Andrews GCRF fund to undertake a pilot project build Illumina sequencing capacity at the Microbiology lab at Makerere University in Kampala.
- The mobile genetic elements of E. coli, utilising long read technology to look at plasmids. This has highlighted the multiple events of horizontal gene transfer that have occurred in the successful epidemic ST131 clone circulating in Scotland. The study has also demonstrated the close linkage of different antibiotic resistance determinants on mobile genetic elements, and therefore the genetic basis of co-selection in response to antibiotic usage.
- Sequencing of a selected number of carbapenemase producing Enterobacteriaceae (CPE) from the AMR Reference laboratory highlighted the distribution of New Delhi Metalloproteinases (NDM) on diverse plasmids circulating in Scotland, which have their origins outside of Europe. The study also identified Klebsiella strains containing genes associated with a ‘hypervirulent’ phenotype that was originally described in the Far East/Australasia, highlighting the global spread and convergence of antibiotic resistance and increased virulence in this invasive pathogen.
- Pairwise sequencing of urinary specimens and associated blood cultures, and sequencing of multiple colonies from a single sample of urine and blood isolates has shown the large amount of variation within the E. coli population.