Thursday, March 1, 2012

Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock

Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock

Lance B. Pricea, Marc Steggerb, Henrik Hasmanc, Maliha Aziza, Jesper Larsenb, Paal Skytt Andersenb, Talima Pearsond, Andrew E. Watersa, Jeffrey T. Fosterd, James Schuppa, John Gillecea, Elizabeth Driebea, Cindy M. Liua,d, Burkhard Springere, Irena Zdovcf, Antonio Battistig, Alessia Francog, Jacek Żmudzkih, Stefan Schwarzi, Patrick Butayej,k, Eric Jouyl, Constanca Pombam, M. Concepción Porreron, Raymond Ruimyo, Tara C. Smithp, D. Ashley Robinsonq, J. Scott Weeser, Carmen Sofia Arriolas, Fangyou Yut, Frederic Laurentu, Paul Keima,d, Robert Skovb, and Frank M. Aarestrupc

+ Author Affiliations


Address correspondence to Lance B. Price,

Editor Fernando Baquero, Ramón y Cajal University Hospital


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.


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.


Citation Price LB, et al. 2012. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. mBio 3(1):e00305-11. doi:10.1128/mBio.00305-11.

Received 19 December 2011 Accepted 3 January 2012 Published 21 February 2012 Copyright © 2012 Price et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.


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