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Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. are the most common causes of central line infection, and Dr. Hostetter has identified heparin binding motifs in surface-associated proteins in these organisms that mediate biofilm formation. Using C. albicans as the prototype organism, she has shown that heparin that is present as an anticoagulant in central lines binds to the microbial surface proteins, and mutation of residues in a single heparin binding motif within these proteins prevents biofilm formation. A polyclonal IgG recognizing the motif stops biofilm formation in a rat model, while control IgG has no effect. These results show the efficacy of peptides or monoclonal antibodies in preventing biofilm formation and central line associated bloodstream infections.
Prosthetic orthopedic procedures: It is not atypical for patients to develop infections on the surface of implanted orthopedic prosthetics (knee replacements, hip replacements, and similar). Like cardiac procedures, heparin sulfate is often used to prevent Deep Vein Thrombosis, which similarly “attracts” the organisms that typically cause the infection mediated via the heparin binding motif. Again, the accepted clinical protocol may actually exacerbate the infection risk, and the antibody could potentially mitigate infection risk for this population/procedure.
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Pending PCT ApplicationPCT/US13/31499Priority Date: 04/20/2012Will File Worldwide Coverage
Lead InvestigatorMargaret Hostetter, MDAlbert B. Sabin ProfessorDirector, Division of Infectious Diseases
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Click image for caption.
Top panels (A) show a heparinized jugular venous catheter removed from a Sprague Dawley rat 24 hours after injection of C. albicans incubated with pre-immune lgG.
Bottom panels (B) show a heparinized jugular venous catheter removed from a Sprague Dawley rat 24 hours after injection of C. albicans incubated with post-immune, affinity purified lgG recognizing heparin binding motif #1.
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