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Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10596-E10604. doi: 10.1073/pnas.1702472114. Epub 2017 Nov 20.

Origin, evolution, and global transmission of community-acquired Staphylococcus aureus ST8.

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Institute of Hygiene, University Hospital Münster, DE 48149 Münster, Germany.
Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, DK 2300 Copenhagen, Denmark.
Pathogen Genomics Division, Translational Genomics Research Institute, Flagstaff, AZ 86005.
Department of Paraclinical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago.
Department of Microbiology, Centre de Recherches Médicales de Lambaréné, GA 242 Lambaréné, Gabon.
Institute of Tropical Medicine, German Center for Infection Research, Eberhard Karls University, DE 72076 Tübingen, Germany.
Faculty of Medicine, University Hospital of Pointe-à-Pitre, University of the French West Indies, 97110 Pointe-à-Pitre, Guadeloupe, France.
Unité Environnement et Santé, Institut Pasteur de Guadeloupe, 97110 Pointe-à-Pitre, Guadeloupe, France.
School of Veterinary and Laboratory Sciences, Murdoch University, Western Australia, Australia, 6150.
PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia, Australia 6150.
Department of Bacteriology, Noguchi Memorial Institute for Medical Research, LG581 Accra, Ghana.
National Reference Center for Staphylococci, Hospices Civils de Lyon, University of Lyon, FR 69002 Lyon, France.
Institute for Medical Microbiology and Hygiene, Technical University of Dresden, DE 01307 Dresden, Germany.
Alere Technologies, DE 07749 Jena, Germany.
Institute of Medical Microbiology, University Hospital Münster, DE 48149 Münster, Germany.
Clinical Microbiology, Medizinisches Versorgungszentrum SYNLAB Leverkusen GmbH, DE 51375 Leverkusen, Germany.
National Reference Centre for Staphylococci and Enterococci, Wernigerode Branch, Robert-Koch-Institut, DE 38855 Wernigerode, Germany.
Institute of Hygiene, University Hospital Münster, DE 48149 Münster, Germany;


USA300 is a pandemic clonal lineage of hypervirulent, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) with specific molecular characteristics. Despite its high clinical relevance, the evolutionary origin of USA300 remained unclear. We used comparative genomics of 224 temporal and spatial diverse S. aureus isolates of multilocus sequence type (ST) 8 to reconstruct the molecular evolution and global dissemination of ST8, including USA300. Analyses of core SNP diversity and accessory genome variations showed that the ancestor of all ST8 S. aureus most likely emerged in Central Europe in the mid-19th century. From here, ST8 was exported to North America in the early 20th century and progressively acquired the USA300 characteristics Panton-Valentine leukocidin (PVL), SCCmec IVa, the arginine catabolic mobile element (ACME), and a specific mutation in capsular polysaccharide gene cap5E Although the PVL-encoding phage ϕSa2USA was introduced into the ST8 background only once, various SCCmec types were introduced to ST8 at different times and places. Starting from North America, USA300 spread globally, including Africa. African USA300 isolates have aberrant spa-types (t112, t121) and form a monophyletic group within the clade of North American USA300. Large parts of ST8 methicillin-susceptible S. aureus (MSSA) isolated in Africa represent a symplesiomorphic group of ST8 (i.e., a group representing the characteristics of the ancestor), which are rarely found in other world regions. Isolates previously discussed as USA300 ancestors, including USA500 and a "historic" CA-MRSA from Western Australia, were shown to be only distantly related to recent USA300 clones.


Africa; CA-MRSA; USA300; comparative genomics; molecular evolution

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