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

By L. Price, M. Stegger, Henrik Hasman, Maliha Aziz, J. Larsen, P. Andersen, Talima R. Pearson, Andrew E. Waters, J. Foster, J. Schupp and 23 more. mBio, 2012

869 citations recorded by the source corpus.

ABSTRACT 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. 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.

Subfields: Agronomy and Crop Science, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3628465ee38b084f359df31cb3312e632e56b0f0

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Citations in the corpus

Staphylococcus aureus and Staphylococcal Food-Borne Disease: An Ongoing Challenge in Public Health (2014, background): “In the United States, approximately 30% and 1.5% of the population are colonized with methicillin-susceptible S. aureus (MSSA) [43] and MRSA, respectively, [43–45] with the most important site for colonization being the anterior nares (nostrils) [46].”
Deep learning improves antimicrobial peptide recognition (2018, background): “Antimicrobial resistance remains a serious problem for humans and livestock around the world, as more drugs lose sensitivity to the pathogens they were designed to eliminate (Price et al. , 2012; U.S. Department of Health and Human Services, 2013; World Health Organization, 2014).”
Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology (2018, background): “human MSSA strain that acquired tetracycline and methicillin resistance (822).”
Solving the Problem of Comparing Whole Bacterial Genomes across Different Sequencing Platforms (2014, methodology): “For Staphylococcus aureus CC398, the completely sequenced and annotated strain SO385 (AM990992.”
Diverse and abundant antibiotic resistance genes in Chinese swine farms (2013, neutral): “microb Agents Chemother 49(8):3541–3543.”
Horizontal Gene Transfer (2015, background): “Price LB, Stegger M, Hasman H et al. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock.”