Ventricular assist devices (VADs) are an important part of the treatment of advanced heart failure. They sustain patients until cardiac transplantation or recovery and are also approved as "destination therapy" for those ineligible for transplant. As donor hearts are in short supply, VADs have the potential to become a routine substitute for transplantation. However, the use of VADs is limited by the high frequency of infection, which occurs in 18-59% of cases. VAD-related infections are difficult to diagnose and the clinical and epidemiologic assessment of these infections is limited by the lack of universally accepted diagnostic criteria. Using data from a multi-center, prospective study of VAD recipients, we will develop diagnostic criteria for VAD infections that we aim to validate for use by other investigators and clinicians. There is also limited information on the pathogenesis and molecular epidemiology of Staphylococcus epidermidis, the most common pathogen associated with these infections. Its prominent role may be due to its ubiquitous presence as a skin and nares colonizer and its ability to adhere to and form biofilms on prosthetic devices. We will evaluate samples of S. epidermidis colonizing VAD patients to determine the role of S. epidermidis commensal flora in the subsequent development of VAD-related infection. We will determine strains'antibiotic susceptibility and describe their genetic relatedness using techniques such as pulsed-field gel electrophoresis. We will explain how these factors change over time. We also aim to identify virulence determinants that contribute to the ability of particular S. epidermidis strains to cause VAD-related infections. To do this, we will use microarray analyses to compare infection and commensal isolates in order to identify genes associated with infection. These potential virulence genes will be investigated in additional studies. Our findings may help elucidate potential vaccine or therapeutic targets. This research will be essential to my career development as a faculty in infectious diseases and epidemiology who specializes in Staphylococcal molecular epidemiology and pathogenesis. Relevance: Heart-assist devices are frequently infected with bacteria such as Staphylococcus epidermidis. These infections are difficult to diagnose and we have limited understanding of how and why they occur. This research will improve the diagnosis of these infections and will identify the genes responsible for them so that vaccines and new treatments can be developed.