Genome-Wide Analysis of S. Aureus Strains to Identify Variants Associated with Infection vs. Colonization

Abstract

S. Aureus is an opportunistic pathogen that asymptomatically colonizes its host, but can cause diseases that range in severity from skin and soft-tissue infections (SSTI) to life-threatening cases of pneumonia and endocarditis. The bacterial factors associated with S. Aureus acquisition, infection, and severity are poorly understood. We sequenced the complete genomes of 144 S. Aureus isolates from patients with either nasal colonization or SSTIs who presented to 10 primary care clinics in South Texas. We then conducted a Genome-Wide Association Study (GWAS) to identify genetic loci that were significantly associated with infection vs. colonization. Significance levels were corrected for multiple tests using the false discovery rate (FDR) procedure. A hierarchical clustering approach was used to estimate the population structures and used as covariates for GWAS stratification. A Random Forest method was used to build a predictive model. The proportions of accurate predictions of phenotypes were reported. GWAS identified 529 variants that were associated with infection vs. colonization. After accounting for population structure, 3 variants (2 nonsynonymous SNPs and 1 insertion) remained statistically significant. One SNP was located in a gene encoding for phosphoglycerate mutase, an enzyme responsible for glycolysis. Another SNP was located in a gene encoding a phage portal protein. A third variant was located in an intergenic region between a transposase and the speG gene within the ACME unit. The Random Forest predictive model demonstrated an accuracy of >88% (misclassification rate of <12%). The candidate loci identified in this study provide a resource for biological studies of S. Aureus pathogenicity. Ultimately, a better understanding of genetic factors associated with disease severity could aid in the management and prevention of S. Aureus infections. All authors: No reported disclosures.