Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major problem, being observed outside healthcare settings as a cause of infection in young individuals without prior healthcare exposures. In several US cities, CA-MRSA is now responsible for the majority of community-onset skin infections and is endemic. Prior work by this research team has demonstrated that HIV-infected patients are at high risk for CA-MRSA colonization and infection and that the basis for this risk may be individual behavioral factors rather than immune status. We have shown that incarceration is a major risk for CA-MRSA in HIV- infected and HIV-negative individuals and that residence in high detainee release zip codes is associated with increased risk for developing a MRSA infection; however, there remains a gap in knowledge about optimal strategies to halt the spread of MRSA outside of healthcare settings. Jails are unique settings characterized by high turnover, high recidivism, and high rates of release into community areas marked by some of the highest levels of poverty in the US. These characteristics make the jail an optimal site for implementing interventions aimed at benefiting both detainees and the community at large. Several prior interventions for sexually transmitted diseases have demonstrated that an intervention in the jail can have significant downstream benefits in the community as the jail provides an opportunity to intervene with a difficult-to-reach population that often lacks access to medical care following release. We believe that this type of framework could be extended to MRSA to maximize the benefits of a non-hospital intervention. Funds are therefore requested to examine the genomic epidemiology of MRSA strains in a jail setting. We will screen individuals for MRSA carriage at nasal and extra-nasal body sites at admission to the jail and 30 days into incarceration. We will determine a rate of MRSA acquisition in the jail and use whole genome sequencing (WGS) to discriminate between endemic MRSA strains. We will integrate genome data with epidemiologic data gathered from a well- established electronic surveillance data warehouse that includes detainee locations and a streamlined electronic survey instrument to determine if host factors and common exposures during incarceration facilitate transmission of MRSA. The proposal has three aims: (1) Determine the prevalence of MRSA colonization and the range of genetic diversity of MRSA strains entering jail, (2) Define the acquisition rate of MRSA in jail and identify predictors of acquisition, and (3) Determine if MRSA strains acquired during incarceration are genetically similar and identify if there are jail exposures that facilitaed acquisition of MRSA. This innovative project will extend the use of WGS as an epidemiologic tool to a jail setting and use generated genome data to inform a site-specific MRSA prevention strategy in the jail. Given the central role the jail is hypothesized to play in propagating the spread of MRSA to high-poverty, inner-city neighborhoods, our proposal has significant