Staphylococcus aureus is an important opportunistic pathogen in humans and animals. In humans, there has been an increase in community-associated methicillin-resistant Staphylococcus aureus (MRSA) causing disease in healthy humans. The exact evolutionary origins and basis for its recent expansion are not yet clear. In livestock, S. aureus is an important cause of diseases of welfare and economic importance, including bovine mastitis. Molecular typing studies demonstrate that natural populations of S. aureus are highly clonal and largely adapted to a specific host, however there are some lineages that colonise multiple host species. In particular, clonal complex 97 (CC97) is a dominant bovine mastitis-associated lineage which has been isolated from other animal species, and more recently there are increasing reports of CC97 S. aureus from human infections worldwide. The basis for this wide host tropism is currently unknown. In order to investigate the evolutionary origins of S. aureus CC97, 43 strains were selected for whole genome sequencing, isolated from humans, cattle and pigs, from 18 different countries on 4 continents, ranging from 1956 to 2012. Phylogenetic analysis using high quality core genome single nucleotide polymorphisms (SNPs) resolved the single CC97 lineage into host-adapted sublineages, which were likely the result of 2 independent livestock-to-human host jumps estimated to have occurred at least 40 years ago. One of the human sublineages consisted of strains from 4 continents indicating global dissemination since the host jump occurred. In order to investigate the genetic basis for human host adaptation in S. aureus CC97, comparative genomic analysis of mobile genetic elements, nonsynonymous SNPs and small insertions and deletions was performed. Of note, independent acquisitions of genetic elements encoding antimicrobial resistance and specific mediators of human innate immune evasion were identified in the human-adapted S. aureus CC97 strains. These data are consistent with an important role for mobile genetic elements in the host adaptive evolution of S. aureus CC97. Also in the current study, a bovine-associated single locus variant of ST97 (ST71) was identified as a phylogenetic outgroup relative to all other S. aureus CC97 strains examined. Comparative genomic analysis of ST71 strains with representative bovine ST97 strains indicate that ST71 has a mosaic genome. A large region spanning the origin of replication demonstrated closest homology to non-CC97 ruminant-associated genotypes, with the remainder of the genome consistent with an ancestral ST97 genetic background. Recombination detection analysis predicts that one or more large-scale recombination events have occurred in the region that spans the origin of replication, resulting in variation in gene content between ST71 and ST97. The data highlight the potential role of homologous recombination in rapidly generating genomic diversity that might alter the phenotype of strains in the ecological niche of the bovine mammary gland. Overall, the study reveals the evolutionary history of a major pathogenic clone of S. aureus affecting multiple host species, and identifies the genetic events which have contributed to its success.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:693675 |
| Date | January 2015 |
| Creators | Spoor, Laura Elizabeth |
| Contributors | Fitzgerald, Ross ; Faulkner, Geoff |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/16216 |
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