Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive <named-content content-type="genus-species">Staphylococcus aureus</named-content> in Europe
David M. Aanensen,
Edward J. Feil,
Matthew T. G. Holden,
Janina Dordel,
Corin A. Yeats,
Artemij Fedosejev,
Richard Goater,
Santiago Castillo-Ramírez,
Jukka Corander,
Caroline Colijn,
Monika A. Chlebowicz,
Leo Schouls,
Max Heck,
Gerlinde Pluister,
Raymond Ruimy,
Gunnar Kahlmeter,
Jenny Åhman,
Erika Matuschek,
Alexander W. Friedrich,
Julian Parkhill,
Stephen D. Bentley,
Brian G. Spratt,
Hajo Grundmann
Affiliations
David M. Aanensen
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom
Edward J. Feil
The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
Matthew T. G. Holden
School of Medicine, University of St. Andrews, St. Andrews, United Kingdom
Janina Dordel
Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
Corin A. Yeats
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom
Artemij Fedosejev
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom
Richard Goater
The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Santiago Castillo-Ramírez
Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de Mexico, Cuernavaca, Morelos, Mexico
Jukka Corander
Helsinki Institute for Information Technology HIIT, Aalto, Finland
Caroline Colijn
Department of Mathematics, Imperial College London, London, United Kingdom
Monika A. Chlebowicz
Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands
Leo Schouls
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Max Heck
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Gerlinde Pluister
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Raymond Ruimy
Centre Hospitalier Universitaire de Nice, Nice, France
Gunnar Kahlmeter
EUCAST Development Laboratory, Växjö, Sweden
Jenny Åhman
EUCAST Development Laboratory, Växjö, Sweden
Erika Matuschek
EUCAST Development Laboratory, Växjö, Sweden
Alexander W. Friedrich
Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands
Julian Parkhill
Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
Stephen D. Bentley
Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
Brian G. Spratt
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom
Hajo Grundmann
Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands
ABSTRACT The implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http://www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show that in silico predictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) community-oriented database infrastructure and analysis tools. IMPORTANCE The spread of antibiotic-resistant bacteria is a public health emergency of global concern, threatening medical intervention at every level of health care delivery. Several recent studies have demonstrated the promise of routine whole-genome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control. However, as this technology becomes more widely adopted, the key challenges of generating representative national and international data sets and the development of bioinformatic tools to manage and interpret the data become increasingly pertinent. This study provides a road map for the integration of WGS data into routine pathogen surveillance. We emphasize the importance of large-scale routine surveys to provide the population context for more targeted or localized investigation and the development of open-access bioinformatic tools to provide the means to combine and compare independently generated data with publicly available data sets.