Abstract

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health-care associated infections, particularly bloodstream infections (BSI). Concomitant colonization of the anterior nares has been shown to have implications on persistence, recurrence, and transmission events. We performed genomic comparisons between paired nasal and blood MRSA isolates obtained from the same patient to elucidate the genetic differences that may contribute to within-host invasion and virulence. Methods Patients hospitalized with MRSA bloodstream infection were swabbed in the bilateral nares. Paired blood and nasal isolates underwent DNA extraction and spa typing. Nasal and blood isolates from the same patients with matching spa types were sequenced by Illumina and PacBio respectively. For genomic analysis, PathoSPOT and Snippy were used to compare genomes of nasal and blood isolate pairs to evaluate single nucleotide polymorphisms, insertions and deletions. Results Of 121 patients with MRSA BSI, 87 patients (72%) had concomitant colonization of the anterior nares with MRSA. Spa type of t002 predominated in both blood and nasal isolates. From the 76 pairs that underwent genomic analysis, several mutated genes were identified across all pairwise comparisons, 8 of which recurred in more than one patient pair. These included genes involved in conferring antibiotic resistance, increased mutability, immune evasion, and adaptive metabolism. Conclusion In patients with MRSA BSI and concomitant MRSA nasal colonization, mutations identified by genomic analysis in blood-nasal pairs are implicated in contributing to invasion and within-host adaptability. Disclosures All Authors: No reported disclosures.

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