Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive Staphylococcus aureus in Europe
Authors: Aanensen David M. , Feil Edward J. , Holden Matthew T. G. , Dordel Janina , Yeats Corin A. , Fedosejev Artemij , Goater Richard , Castillo-Ramírez Santiago , Corander Jukka , Colijn Caroline , Chlebowicz Monika A. , Schouls Leo , Heck Max , Pluister Gerlinde , Ruimy Raymond , Kahlmeter Gunnar , Åhman Jenny , Matuschek Erika , Friedrich Alexander W. , Parkhill Julian , Bentley Stephen D. , Spratt Brian G. , Grundmann Hajo ,   European SRL Working Group, Mittermayer Helmut , Krziwanek Karina , Stumvoll Sabine , Koller Walter , Denis Olivier , Struelens Marc , Nashev Dimitr , Budimir Ana , Kalenic Smilja , Pieridou-Bagatzouni Despo , Jakubu Vladislav , Zemlickova Helena , Westh Henrik , Larsen Anders Rhod , Skov Robert , Laurent Frederic , Ettienne Jerome , Strommenger Birgit , Witte Wolfgang , Vourli Sofia , Vatopoulos Alkis , Vainio Anni , Vuopio-Varkila Jaana , Fuzi Miklos , Ungvári Erika , Murchan Stephan , Rossney Angela , Miklasevics Edvins , Balode Arta , Haraldsson Gunnsteinn , Kristinsson Karl G. , Monaco Monica , Pantosti Annalisa , Borg Michael , van Santen-Verheuvel Marga , Huijsdens Xander , Marstein Lillian , Jacobsen Trond , Simonsen Gunnar Skov , Airesde-Sousa Marta , de Lencastre Herminia , Luczak-Kadlubowska Agnieszka , Hryniewicz Waleria , Straut Monica , Codita Irina , Perez-Vazquez Maria , Iglesias Jesus Oteo , Spik Vesna Cvitkovic , Mueller-Premru Manica , Haeggman Sara , Olsson-Liljequist Barbro , Ellington Matthew , Kearns Angela 
Published: May 2016

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.