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



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Price, Lance B and Stegger, Marc and Hasman, Henrik and Aziz, Maliha and Larsen, Jesper and Andersen, Paal Skytt and Pearson, Talima and Waters, Andrew E and Foster, Jeffrey T and Schupp, James and Gillece, John and Driebe, Elizabeth and Liu, Cindy M and Springer, Burkhard and Zdovc, Irena and Battisti, Antonio and Franco, Alessia and Zmudzki, Jacek and Schwarz, Stefan and Butaye, Patrick and Jouy, Eric and Pomba, Constanca and Porrero, M Concepción and Ruimy, Raymond and Smith, Tara C and Robinson, D Ashley and Weese, J Scott and Arriola, Carmen Sofia and Yu, Fangyou and Laurent, Frederic and Keim, Paul and Skov, Robert and Aarestrup, Frank M (2012) Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. mBio, 3 (1). ISSN 2150-7511

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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.

Item Type:Article
Subjects:Medical sciences > Veterinary
ID Code:39671
Deposited On:21 Dec 2016 12:46
Last Modified:21 Dec 2016 12:46

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