Genomic Epidemiological Insights Into MRSA Transmission and Adaptation in an Urban Jail and the Surrounding Community
Creators: name: Thiede, Stephanie
Publisher: name: My University
Year: 2021
Subjects: subject: genomic epidemiology
subject: MRSA
subject: community transmission
subject: jail
subject: bacterial evolution
subject: Microbiology and Immunology
subject: Science

description: Antibiotic resistant pathogens pose a global health threat as resistance continues to evolve and spread across the globe. One such pathogen, methicillin-resistant Staphylococcus aureus (MRSA) causes about 300,000 cases and 10,000 deaths annually in the United States. MRSA once exclusively caused infections among hospitalized patients with known risk factors. Around 1999, a new lineage called USA300 emerged to cause infection in otherwise healthy individuals in the community in the United States. Since then, infection control efforts have been effective at steadily reducing MRSA rates in the healthcare setting. However, these reductions are strain-specific and MRSA transmission in the community remains a problem. Efforts to reduce community MRSA transmission require in-depth knowledge of how and where MRSA is circulating in the community. In this dissertation, we explored MRSA adaptation and transmission in the urban community of Chicago and in a large, inner-city jail in Chicago. Leveraging a comprehensive collection of clinical MRSA cultures from 2011-2014, we first applied genomic epidemiology methods to determine the contributions of the community and healthcare settings in MRSA USA300 spread. We found a lack of healthcare overlap among individuals with genetically similar MRSA strains, even among so-called "healthcare-associated" or "hospital-onset" infections. This finding implicated the community in acquisition of USA300 MRSA and merits further studies to pinpoint areas of the community to target. Next we honed in on one sector of the community with increased burden of MRSA: a large, urban jail. We found significant importation of MRSA into the jail, with 19% of individuals entering the jail colonized, as compared to the national nasal carriage prevalence of 1.5%. Moreover, by following individuals longitudinally we found that MRSA was also acquired within the jail, with ~8% of intake negative individuals screening positive by 30 days. Further, genomic analysis of individuals acquiring MRSA infections in jail revealed evidence of transmission mediated by spatiotemporal overlap in the jail and persistent environmental contamination, pointing to potential targets to reduce transmission. Finally, we uncovered an antibiotic resistance-conferring plasmid that was independently acquired multiple times and was associated with increased transmission both in the jail and in the community. The prevalence of the plasmid was much higher in jail-onset infections compared to imported MRSA, suggesting an increased selective pressure in the jail. In the community, the plasmid was associated with incarceration and drug use, suggesting possible acquisition in the jail and potentially reflective of an increased selective pressure for the plasmid in the jail. In this dissertation, we produced insights into USA300 MRSA epidemiology by applying genomic epidemiology approaches to identify sites and risk factors for community transmission. In particular, our integration of genomic and epidemiological data improved our understanding of transmission pathways in the community, in the jail, and the relationship between the two by identifying a variant selected for in the jail that may be spread to the larger community. Moreover, our delineation of community transmission networks feeding into the jail highlights the need to study additional sectors of the community for MRSA transmission. Finally, we provide an analytical framework for genomic epidemiology in jails, which has subsequently been useful to study transmission dynamics of COVID-19 in the jail population.