RT Journal Article T1 Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock A1 Price, Lance B A1 Stegger, Marc A1 Hasman, Henrik A1 Aziz, Maliha A1 Larsen, Jesper A1 Andersen, Paal Skytt A1 Pearson, Talima A1 Waters, Andrew E A1 Foster, Jeffrey T A1 Schupp, James A1 Gillece, John A1 Driebe, Elizabeth A1 Liu, Cindy M A1 Springer, Burkhard A1 Zdovc, Irena A1 Battisti, Antonio A1 Franco, Alessia A1 Zmudzki, Jacek A1 Schwarz, Stefan A1 Butaye, Patrick A1 Jouy, Eric A1 Pomba, Constanca A1 Porrero, M Concepción A1 Ruimy, Raymond A1 Smith, Tara C A1 Robinson, D Ashley A1 Weese, J Scott A1 Arriola, Carmen Sofia A1 Yu, Fangyou A1 Laurent, Frederic A1 Keim, Paul A1 Skov, Robert A1 Aarestrup, Frank M AB UNLABELLEDSince 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.IMPORTANCEModern 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. PB American Society for Microbiology SN 2150-7511 YR 2012 FD 2012 LK https://hdl.handle.net/20.500.14352/45171 UL https://hdl.handle.net/20.500.14352/45171 LA eng DS Docta Complutense RD 25 abr 2025