Revolutionising Public Health Reference Microbiology using Whole Genome Sequencing: Salmonella as an exemplar

Abstract

Advances in whole genome sequencing (WGS) platforms and DNA library preparation have led to the development of methods for high throughput sequencing of bacterial genomes at a relatively low cost (Loman et al. 2012; Medini et al. 2008). WGS offers unprecedented resolution for determining degrees of relatedness between strains of bacterial pathogens and has proven a powerful tool for microbial population studies and epidemiological investigations (Harris et al. 2010; Lienau et al. 2011; Holt et al. 2009; Ashton, Peters, et al. 2015). The potential utility of WGS to public health microbiology has been highlighted previously (Koser et al. 2012; Kwong et al. 2013; Reuter et al. 2013; Joensen et al. 2014; Nair et al. 2014; Bakker et al. 2014; DAuria et al. 2014). Here we report, for the first time, the routine use of WGS as the primary test for identification, surveillance and outbreak investigation by a national reference laboratory. We present data on how this has revolutionised public health microbiology for one of the most common bacterial pathogens in the United Kingdom, the Salmonellae.\n\nDATA SUMMARY1. PHE Salmonella sequencing data is deposited in the Sequence Read Archive in BioProject PRJNA248792.\n\nIMPACT STATEMENTThe first human genome cost around $3 billion, and took around 10 years to complete. Advances in DNA sequencing technology (also referred to as whole genome sequencing (WGS)) allow the same feat to be accomplished today for less than $10000 and less than 2 weeks. This remarkable improvement in technology has also led to a step change in microbiology, increasing our understanding of the evolution of major human pathogens such as Yersinia pestis, Salmonella Typhi and Mycobacterium tuberculosis. While these kinds of academic studies provide unparalleled context for public health action, until now, this approach has not been routinely employed at the frontline. At Public Health England, WGS has been implemented for routine public health identification, characterisation and typing of an important human pathogen, Salmonella, replacing methods that have changed little over the last 100 years. Analysis of WGS data has identified outbreaks that were previously undetectable and been used to infer rare antimicrobial resistance patterns. This paper will serve as a notification to the community of the methods PHE are using, and will be of great use to other public health labs considering switching to WGS.