title: Inhibition of staphylococcal wound infection and potentiation of antibiotic prophylaxis by a recombinant fragment of the fibronectin-binding protein of Staphylococcus aureus.
abstract: Adherence of Staphylococcus aureus to host tissues is a critical step for colonization and initiation of infection. The fibronectin-binding proteins (FnBPs) of S. aureus have been implicated in adherence and internalization in nonprofessional phagocytes. A recombinant fragment of the fibronectin-binding domains (rFnBF) that potently inhibits S. aureus entry into host cells was generated. To test the hypothesis that rFnBF may attenuate the establishment of infection, the ability of intermuscularly administered rFnBF to prevent abscess formation was determined in a guinea pig model of wound infection. rFnBF exhibited dose-dependent inhibition of abscess formation and, at a 100-microg dose, raised the median infective dose approximately 170-fold, compared with the control. In addition, rFnBF potentiated the benefit of prophylaxis with cefazolin. Thus, exogenous administration of the fibronectin-binding domain of FnBP reduces the risk of staphylococcal abscess formation and should be investigated further as a novel agent for prevention of wound infection.
authors.affiliation: Medical Research Service, Department of Veterans Affairs, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. bmenzies@u.washington.edu
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Menzies
authors.forename: Yordanka
authors.initials: Y
authors.lastname: Kourteva
authors.forename: Allen B
authors.initials: AB
authors.lastname: Kaiser
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kernodle
mesh_terms: D018829:Adhesins, Bacterial; D000818:Animals; D019072:Antibiotic Prophylaxis; D001426:Bacterial Proteins / Q000235:genetics / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics / Q000627:therapeutic use*; D002437:Cefazolin / Q000627:therapeutic use; D002478:Cells, Cultured; D002511:Cephalosporins / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D014471:Umbilical Veins; D014946:Wound Infection / Q000517:prevention & control*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D011994:Recombinant Proteins; C078635:fibronectin-binding proteins, bacterial; D002437:Cefazolin