Staphylococcus aureus is a commensal and pathogen of humans and other animals. Disease with S. aureus is complicated by dissemination of antimicrobial resistance, including methicillin resistance. Methicillin resistant S. aureus (MRSA) is a significant burden on the health care industry (HA-MRSA); however, in recent years, public health concern has arisen from isolates harbored in the community (CA-MRSA) and livestock species (LA-MRSA). Concerns with LA-MRSA isolates are the direct impact of infection with livestock isolates and indirect impacts of genetic transfer of virulence or antimicrobial resistance genes from LA-MRSA isolates. The prototypical LA-MRSA strain, sequence type (ST) 398, is considered less virulent than HA- and CA-MRSA isolates. Reduced virulence of LA-MRSA ST398 isolates is attributed to loss of human specific virulence factors and reduced colonization and transmission in humans. While LA-MRSA ST398 isolates are common in European swine, LA-MRSA isolates in the United States are diverse including ST398, ST9, and ST5. LA-MRSA ST5 elevated public health concerns, because, unlike MRSA ST398 and ST9, MRSA ST5 is a globally disseminated and highly pathogenic lineage.

To better understand direct and indirect impact of swine associated LA-MRSA ST5, this thesis investigated the genetics of swine associated and clinical MRSA ST5 isolates. Phylogenetic analysis revealed LA-MRSA ST5 isolates are genetically distinct from clinical MRSA ST5 isolates, which was confirmed by differences in virulence and antimicrobial resistance genes harbored on mobile genetic elements. LA-MRSA ST5 isolates lacked immune evasion genes harbored by the β-hemolysin converting bacteriophage and resistance genes differed between swine associated and clinical MRSA ST5 isolates, which indicated genetic exchange was unlikely between the screened populations. Resistance genes were consistent with selective pressures from antimicrobial use in the swine industry and hospital environment. Finally, swine associated and clinical MRSA ST5 isolates adhered equivalently to human keratinocytes, although LA-MRSA ST5 isolates lacked virulence factors contributing to colonization. These results indicate the isolates screened were distinct with no evidence of mobile genetic element transfer between subsets. The virulence of LA-MRSA ST5 isolates is expected to be reduced as compared to clinical MRSA ST5 isolates due to the absence of genes that contribute to disease in humans.