Investigation published in mBio

February 21^st, 2012

Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production. IMPORTANCE: Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional
zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production

Price LB., Stegger M., Hasman H., Aziz M., Larsen JL., Andersen PS., Pearson T., Waters AE., Foster JT., Schupp J., Gillece J., Driebe E., Liu CM., Springer B., Zdovc I., Battisti A., Franco A., Zmudzki J., Schwarz S., Butaye P., Jouy E., Pomba MC., Porrero MC., Ruimy R., Smith TC., Robinson DA., Weese JS., Arriola CS., Yu F., Laurent F., Keim P., Skov R. and Aarestrup F.

Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock

Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock

	Servicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).
	Pathogen Genomics Division. Translational Genomics Research Institute (TGEN).
	Department of Microbiological Surveillance and Research. Statens Serum Institut (SSI).
	National Food Institute (DTU Food). Technical University of Denmark (DTU).
	Center for Microbial Genetics and Genomics. Northern Arizona University (NAU).
	Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH, Bereich Humanmedizin. Institut für Medizinische Mikrobiologie und Hygiene.
	Institute of Microbiology and Immunology. Faculty of Medicine. University of Ljubljana (UL).
	Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana (IZSLT).
	Department of Swine Diseases. National Veterinary Research Institute (PIWET).
	Institute of Farm Animal Genetics. Friedrich Loeffler Institut-Bundesforschungsinstitut fuer Tiergesundheit (FLI).
	Department of Pathology, Bacteriology, and Poultry Diseases. Faculty of Veterinary Medicine. University of Ghent (UGENT).
	Unit of General Bacteriology. Veterinary and Agrochemical Research Centre (CODA_CERVA).
	Ploufragan Plouzané Laboratory. Agence Nationale de Sécurité Sanitaire de l´alimentation, de l´environnement et du travail (ANSES).
	Interdisciplinary Centre of Research in Animal Health. Faculdade de Medicina Veterinária. Universidade Técnica de Lisboa (UTL).
	Hôpital Bichat-Claude Bernard. Université Paris Diderot.
	Center for Emerging Infectious Diseases. University of Iowa.
	Department of Microbiology. University of Mississippi Medical Center (UMMC).
	Ontario Veterinary College. University of Guelph.
	Facultad de Medicina Veterinaria. Universidad Nacional Mayor de San Marcos.
	Department of Laboratory Medicine. First Affiliated Hospital of Wenzhou Medical College.
	Laboratory of Bacteriology. Hôpital de la Croix Rousse.