Date of Award

5-1-2024

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biological Sciences

Dissertation/Thesis Chair

Cheryl P. Andam

Committee Members

Erica Lasek-Nesselquist, Alex Valm

Keywords

antimicrobial resistance, bloodstream infection, genome, mecA, methicillin resistance, Staphylococcus aureus

Subject Categories

Biology

Abstract

Staphylococcus aureus is a commensal and an opportunistic pathogen that causes a variety of diseases in humans, from minor skin and soft tissue infections to life-threatening invasive diseases. The emergence and spread of multidrug-resistant and methicillin-resistant S. aureus (MRSA) complicate treatment options, which can lead to significant morbidity and mortality of patients. In this study, we compared the clonal lineages and genomic features of bloodstream-derived S. aureus populations from different locations. We leveraged 957 previously published genomes derived from bloodstream infections across six hospitals located in Illinois, Minnesota, Missouri, New Hampshire, and New York, USA. We carried out pan-genome analysis, phylogenetic tree reconstruction, and in silico detection of antimicrobial resistance (AMR) genes. We identified 67 sequence types (STs), with ST5 and ST8 together accounting for 46.18% of the entire dataset. The five populations showed significant differences in genome-wide average nucleotide identity and in the number of AMR genes per genome. We identified a total of 26 distinct AMR genes associated with ten antimicrobial classes. The mobile genetic element SCCmec carrying the mecA gene, which confers resistance to nearly all beta-lactams, was present in 478 genomes and of which 82 are from ST5 and 247 from ST8. The most common SCCmec types were types II and IV, which were detected in all five locations. We find that the distribution of bloodstream-associated S. aureus is shaped by both the clonal expansion of lineages ST5 and ST8 across geographically disparate hospitals and of the sharing of different SCCmec types between lineages. These findings provide critical insights on how invasive S. aureus remains a persistent public health threat, particularly when considering its repository of mobile AMR determinants that can impinge on critical treatment options. Continuous and broader surveillance using whole genome sequencing will be important to track the spread of multidrug resistance.

Download

Included in

Biology Commons

Share

COinS