This is a competitive renewal application requesting funds to continue our studies of Staphylococcus epidermidis, biomaterials and pathogenicity. Adherent strains of S. epidermidis are the most frequent cause of biomaterial-induced infections. It appears that the capacity of coagulase- negative staphylococci to adhere to the surfaces of biomaterials represents an important virulence attribute of these normal flora organisms. The significant features of biomaterial-centered infections are: (1) adherent colonization of surfaces, (2) production of extracapsular polysaccharides, and (3) persistence of infection due to impaired host defense mechanisms. Adhesion to surfaces is believed to depend in part on interactions involving extracapsular polysaccharides, matrix proteins, and the specific atomic geometry and electronic state of the biomaterial surface. Our preliminary studies indicate that attachment of S. epidermidis to biomaterial surfaces most likely involves surface polysaccharides and adhesive host proteins like fibronectin. In the case of titanium alloy, elemental surface segregations of vanadium also appear to favor adherence. In addition, we have observed that macrophages exhibit an impaired phorbol myristate acetate (PMA) -elicited oxidative burst after interaction with polymethylmethacrylate (PMMA). Macrophages exposed to PMMA also failed to respond to macrophage activation factor, which suggests that they are defective in terms of becoming primed. These deficits could explain the impaired killing of S. epidermidis at the biomaterial-tissue interface.
In Aim 1, our preliminary data will be further explored by continuing our isolation, extraction, and purification studies of extracapsular polysaccharides of S. epidermidis RP-12 strain;
in Aim 2, we will identify the dominant fraction(s) involved in primary binding and select the smallest oligosaccharide component which will competitively inhibit the binding of S. epidermidis to biomaterials or conditioning proteins.
In Aim 3. the role of biomaterial (Ti6A14V) surface features (eg elemental segregations) will be evaluated as binding sites for S. epidermidis and for S. epidermidis exopolysaccharide fractions using energy dispersive x-ray analysis correlated with electron microscopy.
In Aim 4, the role of biomaterials (Ti6A14V), polymethylmethacrylate, and polyurethane in phagocyte impairment will be investigated by determinations of oxidative metabolism and killing capacity of macrophages for S. epidermidis in the presence of selected biomaterials.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035939-07
Application #
3289404
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1990-12-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Medical Sciences Research Institute
Department
Type
DUNS #
City
Herndon
State
VA
Country
United States
Zip Code
Gristina, A G (1994) Implant failure and the immuno-incompetent fibro-inflammatory zone. Clin Orthop Relat Res :106-18
Gristina, A G; Shibata, Y; Giridhar, G et al. (1994) The glycocalyx, biofilm, microbes, and resistant infection. Semin Arthroplasty 5:160-70
Giridhar, G; Kreger, A S; Myrvik, Q N et al. (1994) Inhibition of Staphylococcus adherence to biomaterials by extracellular slime of S. epidermidis RP12. J Biomed Mater Res 28:1289-94
Gabriel, B L; Gold, J; Gristina, A G et al. (1994) Site-specific adhesion of Staphylococcus epidermidis (RP12) in Ti-Al-V metal systems. Biomaterials 15:628-34
Giridhar, G; Gristina, A G; Myrvik, Q N (1993) Altered oxidative responses and antibacterial activity of adult rabbit alveolar macrophages exposed to poly(methyl methacrylate). Biomaterials 14:609-14
Barth, E; Myrvik, Q M; Wagner, W et al. (1989) In vitro and in vivo comparative colonization of Staphylococcus aureus and Staphylococcus epidermidis on orthopaedic implant materials. Biomaterials 10:325-8
Gristina, A G; Jennings, R A; Naylor, P T et al. (1989) Comparative in vitro antibiotic resistance of surface-colonizing coagulase-negative staphylococci. Antimicrob Agents Chemother 33:813-6
Myrvik, Q N; Wagner, W; Barth, E et al. (1989) Effects of extracellular slime produced by Staphylococcus epidermidis on oxidative responses of rabbit alveolar macrophages. J Invest Surg 2:381-9
Gristina, A G; Dobbins, J J; Giammara, B et al. (1988) Biomaterial-centered sepsis and the total artificial heart. Microbial adhesion vs tissue integration. JAMA 259:870-4
Voytek, A; Gristina, A G; Barth, E et al. (1988) Staphylococcal adhesion to collagen in intra-articular sepsis. Biomaterials 9:107-10

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