Anti-staphylococcal activities of A. actinomycetemcomitans dispersin B

点击翻译按钮获取中文摘要

The Project Summary/Abstract was modified to reflect the changes described above: A major risk associated with implanted medical devices is their high rate of infection. Bacteria that colonize medical devices form matrix-encased biofilms that resist antimicrobial therapy and are often difficult or impossible to eradicate. The extracellular matrix of Staphylococcus aureus and Staphylococcus epidermidis, the most common device-associated pathogens, contains a sticky polysaccharide named PNAG (poly-N-acetylglucosamine) that mediates surface attachment, intercellular adhesion, biocide resistance and immune evasion. Our laboratory discovered an enzyme (dispersin B) that degrades PNAG. Preliminary studies indicate that dispersin B inhibits staphylococcal biofilm formation, detaches pre-formed staphylococcal biofilms, and sensitizes staphylococcal biofilm cells to antimicrobial killing in vitro. Our hypothesis is that dispersin B will be a clinically useful anti-biofilm agent for the treatment and prevention of staphylococcal biofilm infections in vivo. The goal of the present proposal is to demonstrate that dispersin B acts synergistically with antibiotics to detach and kill S. aureus and S. epidermidis biofilms in vitro. Dispersin B will be tested both in solution in a simulated daily antibiotic catheter lock assay, and loaded onto polyurethane disks, either alone or in combination with antibiotics, in a model for antiinfective device coatings. The antibiotics that we plan to test include tigecycline and vancomycin. The results of the proposed studies will extend our knowledge about the mechanism of PNAGmediated biofilm resistance to specific antibiotics, and will demonstrate the feasibility of using dispersin B as anti-biofilm agent in vivo. Since dispersin B does not kill bacteria or inhibit their growth, dispersin B-based strategies may be less prone to the evolution of resistance than strategies utilizing conventional antibiotics.