Biofilms are surface attached bacterial communities encased in a hydrated matrix of exopolysaccharide. In the body, infecting bacteria form biofilms on medical implants, such as indwelling catheters. In this biofilm mode of growth, they are resistant to antibiotics and attack by the body's immune system. Staphylococcal biofilms are the leading cause of hospital acquired implant-based infections, which result in approximately 30,000 deaths per year. S. epidermidis is the leading cause of these infections. The overall goal of this Fast Track grant is to discover drugs that selectively block the formation of staphylococcal biofilms. These drugs will be used to coat the surfaces of medical implants to prevent biofilm development when implants are placed in patients. Here, in phase I, we will demonstrate the capacity to perform molecular genetic analyses in S. epidermidis; we will develop a cell-based high throughput screen for biofilm development, and we will develop a biofilm reactor system for S. epidermidis. The work in Phase I will provide all the molecular genetic tools and screening methods needed in Phase II for the discovery of potent small molecule inhibitors of staphylococcal biofilm formation.
| Kwasny, Steven M; Opperman, Timothy J (2010) Static biofilm cultures of Gram-positive pathogens grown in a microtiter format used for anti-biofilm drug discovery. Curr Protoc Pharmacol Chapter 13:Unit 13A.8 |
| Sandberg, Johan K; Stoddart, Cheryl A; Brilot, Fabienne et al. (2004) Development of innate CD4+ alpha-chain variable gene segment 24 (Valpha24) natural killer T cells in the early human fetal thymus is regulated by IL-7. Proc Natl Acad Sci U S A 101:7058-63 |
