Enterococci are commensal organisms that inhabit the gastrointestinal tract and rarely cause infections in the healthy host. However, in immunocompromised individuals or in individuals on antibiotic therapy, these organisms can cause serious disease. Hospital-acquired infections by Enterococcus faecalis, especially those associated with intravascular catheters, biliary stents and other implants have increased dramatically in recent years. This trend has likely resulted from high level antibiotic-resistance within this genus coupled with the acquisition of virulence determinants and the ability to form biofilms. It is recognized that biofilm associated bacteria are phenotypically different from planktonic cells and tend to be more resistant to antibiotics and to host immune clearance mechanisms. Innate immunity plays a crucial role in the host response to microbial infections but little is known about the immune response to enterococci and enterococcal biofilms. Our laboratory has identified and characterized two important biofilm enhancing loci in E. faecalis;one specifying the enterococcal surface protein Esp and the other the Bee pilus. Both these factors significantly enhance biofilm formation and adherence of E. faecalis to abiotic surfaces in vitro, but much remains to be learned about their functions in vivo. Our underlying hypothesis in this proposal is that the host innate immune response to biofilm and planktonic E. faecalis is quite different and we will examine this through two specific aims. In aim 1, we will compare in vitro the interaction of professional phagocytes and enterococcal biofilms versus planktonic cells from two different genetic backgrounds, to document bacterial survival, host cell response and influence on biofilm architecture. In aim 2, we propose to examine host-pathogen interactions in vivo using two murine models of biofilm-associated infections. The novelty of these studies will be the utilization of a positron emission tomography /computed tomography (PET/CT) approach to image and follow the time course of infections in real time. These exploratory studies are designed to lead to a better understanding of the host response to biofilm-related enterococcal infections and could ultimately lead to new therapeutic strategies to prevent serious enterococcal infections.

PUBLIC HEALTH RELEVANCE: Hospital-acquired infections by antibiotic-resistant Enterococcus faecalis have risen dramatically in recent years. Greater understanding of the host defense mechanisms that protect against invasive enterococcal disease could provide new ways of controlling enterococcal infections.

R21DE020928

2010-08-15

2013-01-31