Abstract
Whole genome sequencing (WGS) promises to be transformative for the practice of clinical microbiology, and the rapidly falling cost and turnaround time mean that this will become a viable technology in diagnostic and reference laboratories in the near future. The objective of this article is to consider at a very practical level where, in the context of a modern diagnostic microbiology laboratory, WGS might be cost-effective compared to current alternatives. We propose that molecular epidemiology performed for surveillance and outbreak investigation and genotypic antimicrobial susceptibility testing for microbes that are difficult to grow represent the most immediate areas for application of WGS, and discuss the technical and infrastructure requirements for this to be implemented.
Highlights
Advances in whole genome sequencing (WGS) [1,2] have resulted in a reduction in the full economic cost of sequencing a typical bacterial genome to as little as £40
The combination of low cost and rapid turnaround time will mean that pathogen WGS can cross the divide between microbial research and the practice of diagnostic microbiology [3,4,5,6]
This holds the potential to transform our understanding of the evolution of pathogens and the global spread of antimicrobial resistance, a problem identified by the World Health Organization (WHO) as one of the three greatest threats to human health [7]
Summary
Advances in whole genome sequencing (WGS) [1,2] have resulted in a reduction in the full economic cost of sequencing a typical bacterial genome to as little as £40 (from extracted DNA to genome sequence). Agar plates can be delivered, inoculated, incubated, and imaged by fully automated conveyor belt systems, reducing the amount of labour required at each of the multiple steps involved in sample processing This development has been driven by the need to reduce costs while maintaining or increasing throughput, resulting in an on-going transition towards laboratory amalgamation and the expansion of centralised facilities, adoption of around the clock working practices, and a shift in the workforce skill mix towards a greater reliance on assistants and a reduction in the number of qualified laboratory technicians. Isolate collection and batching introduces a delay; second, the turnaround time of at least 1 week for the test itself introduces a further delay (and together, these factors mean that genotyping information does not directly inform the management of the patient from whom the isolate was obtained, or of their contacts); and third, the current tools such as spa-typing and pulsed-field gel electrophoresis have a limited resolution, to differentiate strains belonging to the same bacterial clone (such as EMRSA-15, currently the dominant hospital-associated MRSA clone in the United Kingdom [24])
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