Comparative genomics, antimicrobial resistance determinants, and pathogenicity of community-associated Staphylococcus aureus



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Staphylococcus aureus is a major human pathogen and a global public health issue. It is considered an opportunistic pathogen as it asymptomatically colonizes its host, but can occasionally cause diseases that range in severity from relatively minor skin and soft tissue infections (SSTI) to life-threatening cases of pneumonia and endocarditis. There is a critical need to better understand mechanisms that lead to the evolution, resistance, and severity of S. aureus infections. Bacterial whole genome sequencing (WGS) techniques have offered new insights into S. aureus genomic populations and have the potential to predict antimicrobial resistance and infection severity. This study applied WGS 1) to describe the diversity and distribution of resistance mechanisms among community-associated S. aureus isolates, and 2) to identify S. aureus genetic signatures associated with SSTI isolates and derive a predictive risk model. WGS was performed on S. aureus isolates from patients within 14 primary care clinics in the South Texas Ambulatory Research Network from 2007 to 2015. The bacterial genomes were compared to a reference genome, FPR3757 (USA300 strain) to identify single nucleotide polymorphisms (SNPs). Phylogenetic analyses were conducted using concatenated SNP nucleotides in the core genomes. In the first study, the resistome was assembled by identifying antimicrobial resistance determinants related to the phenotypically derived antibiogram. The findings of this study identified that multidrug-resistant S. aureus isolates have emerged in the South Texas community; approximately one-third were multidrug-resistant. There was an increasing resistance pattern to fluoroquinolones. Furthermore, the genotype demonstrated to be highly predictive of antimicrobial resistance (very major error rate=0% and major error rate=1.4%). These findings highlight the genomic diversity of S. aureus strains in the South Texas community and demonstrate the utility of next generation sequencing to define the diversity and distribution of resistance mechanisms within S. aureus. Further work to explore antimicrobial selective pressures is needed. The second study utilized a bacterial genome-wide association study to identify specific variants associated with S. aureus pathogenicity. This study revealed the heterogeneity of S. aureus SSTI and nasal colonization isolates and identified potentially novel pathogenic mechanisms.