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.

Public Health Relevance

Hospital- and community-acquired staph infections result in nearly 100,000 deaths in the U.S. each year. Staph bacteria produce a layer of slime that enables them to stick to implanted medical devices such as catheters. This project will investigate the use of enzymes to break down the staph slime layer in order to prevent bacteria from attaching to medical devices, thereby preventing infection. This method may be an attractive anti-staph therapy because it could reduce or eliminate the need for conventional antibiotics.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section (DDR)
Program Officer
Huntley, Clayton C
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Medicine & Dentistry of NJ
Schools of Dentistry
United States
Zip Code
Kaplan, J B; Sampathkumar, V; Bendaoud, M et al. (2017) In vitro characterization of biofilms formed by Kingella kingae. Mol Oral Microbiol 32:341-353
Rendueles, Olaya; Kaplan, Jeffrey B; Ghigo, Jean-Marc (2013) Antibiofilm polysaccharides. Environ Microbiol 15:334-46
Banerjee, Anushree; Kaplan, Jeffrey B; Soherwardy, Amenah et al. (2013) Characterization of TEM-1 ?-Lactamase-Producing Kingella kingae Clinical Isolates. Antimicrob Agents Chemother 57:4300-4306
Kaplan, Jeffrey B; LoVetri, Karen; Cardona, Silvia T et al. (2012) Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci. J Antibiot (Tokyo) 65:73-7
Pavlukhina, Svetlana V; Kaplan, Jeffrey B; Xu, Li et al. (2012) Noneluting enzymatic antibiofilm coatings. ACS Appl Mater Interfaces 4:4708-16
Kaplan, Jeffrey B; Izano, Era A; Gopal, Prerna et al. (2012) Low levels of ?-lactam antibiotics induce extracellular DNA release and biofilm formation in Staphylococcus aureus. MBio 3:e00198-12
Bendaoud, Meriem; Vinogradov, Evgeny; Balashova, Nataliya V et al. (2011) Broad-spectrum biofilm inhibition by Kingella kingae exopolysaccharide. J Bacteriol 193:3879-86
Kaplan, Jeffrey B; Jabbouri, Said; Sadovskaya, Irina (2011) Extracellular DNA-dependent biofilm formation by Staphylococcus epidermidis RP62A in response to subminimal inhibitory concentrations of antibiotics. Res Microbiol 162:535-41