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Title: Host-adaptive evolution of Staphylococcus aureus
Author: Lowder, Bethan Victoria
ISNI:       0000 0004 2729 7334
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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Staphylococcus aureus is a notorious human pathogen associated with severe nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry and bovine and ovine mastitis, which are a large economic burden on the broiler chicken and dairy farming industries. The population structure of S. aureus associated with humans has been well studied. However, despite the prevalence of S. aureus infections in broiler flocks, our understanding of the diversity of poultry S. aureus is very limited. In this study, multilocus sequence typing was performed on 48 strains of S. aureus isolated from broiler chickens on farms in 6 countries on 4 different continents, in addition to 9 isolates from different species of reared game and wild birds in Scotland. This was followed by fine scale population genetic analysis of a subset of strains by single nucleotide polymorphism discovery. These studies reveal that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump by a subtype of the worldwide human clonal complex 5 (CC5) clonal lineage unique to Poland. In contrast to human subtypes of the CC5 radiation, which demonstrate strong geographic clustering, the poultry CC5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. In order to establish the molecular basis for avian specificity in the CC5 poultry clade, whole genome sequences were determined for a sequence type 5 (ST5) poultry isolate from Ireland and a basal human associated ST5 MRSA strain from Poland. Sequence analysis revealed that the poultry CC5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. In order to examine the importance of positive selection in the adaptation of S. aureus to poultry and for S. aureus evolution, in general, genome-wide analysis of the ratio of synonymous to non-synonymous substitutions was performed on 30 strains from 3 humans and other animals, from diverse lineages. Positive selection has affected proteins from the majority of functional categories, resulting in diversification of the proteome, metabolome and replication capacity, which may be associated with adaptation of S. aureus to diverse environments. For several proteins, an elevated rate of non-synonymous substitutions unique to animal-associated lineages is consistent with a role for these proteins in host adaptation. Taken together, the results of this study have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. The data highlight the importance of gene acquisition and loss and positive selection in the adaptive evolution of S. aureus.
Supervisor: Ross Fitzgerald, Ross. Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Staphylococcus aureus ; genome ; evolution