title: Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive Staphylococcus aureus in Europe.
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.
  
  
  
  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.
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Aanensen
authors.affiliation: The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.affiliation: School of Medicine, University of St. Andrews, St. Andrews, United Kingdom Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom Department of Biology, Drexel University, Philadelphia, Pennsylvania, USA.
authors.forename: Janina
authors.initials: J
authors.lastname: Dordel
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Corin A
authors.initials: CA
authors.lastname: Yeats
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Artemij
authors.initials: A
authors.lastname: Fedosejev
authors.affiliation: The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Goater
authors.affiliation: Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de Mexico, Cuernavaca, Morelos, Mexico.
authors.forename: Santiago
authors.initials: S
authors.lastname: Castillo-Ramírez
authors.affiliation: Helsinki Institute for Information Technology HIIT, Aalto, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
authors.affiliation: Department of Mathematics, Imperial College London, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Colijn
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Chlebowicz
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Schouls
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Heck
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Pluister
authors.affiliation: Centre Hospitalier Universitaire de Nice, Nice, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Ruimy
authors.affiliation: EUCAST Development Laboratory, Växjö, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kahlmeter
authors.affiliation: EUCAST Development Laboratory, Växjö, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Åhman
authors.affiliation: EUCAST Development Laboratory, Växjö, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Matuschek
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Friedrich
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Julian
authors.identifier: 0000-0002-7069-5958
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands Department of Infection Prevention and Hospital Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany hajo.grundmann@uniklinik-freiburg.de.
authors.forename: Hajo
authors.initials: H
authors.lastname: Grundmann
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D004196:Disease Outbreaks / Q000517:prevention & control; D024881:Drug Resistance, Bacterial / Q000235:genetics; D062665:Epidemiological Monitoring; D005060:Europe / Q000453:epidemiology; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA; D012984:Software; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology* / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity*