Crystal structure of staphylococcus aureus clumping factor a in complex with fibrinogen derived peptide and uses thereof

Abstract

The present invention discloses crystal structure of Staphylococcus aureus Clumping factor A (ClfA) in complex with fibrinogen (Fg) derived peptide. Also, the present invention also discloses the use of this structure in the design of ClfA targeted vaccines and therapeutic agents (including monoclonal antibodies). In addition, the present invention discloses isolated and purified engineered Staphylococcus clumping factor A protein (ClfA) with a stabilized, closed conformation and immunogenic compositions thereof including methods of treating a Staphylococcus infection in an individual.

What is claimed is: 
     
         1 . An anti-MSCRAMM:fibrinogen antibody effective to inhibit MSCRAMM:fibrinogen interaction but does not affect binding of other proteins to fibrinogen. 
     
     
         2 . The anti-MSCRAMM:fibrinogen antibody of  claim 1 , wherein said antibody is generated using peptides comprising MSCRAMM binding region on Fibrinogen, said peptide differing from the native Fibrinogen in at least one amino acid residue. 
     
     
         3 . The anti-MSCRAMM:fibrinogen antibody of  claim 2 , wherein said peptide is P16 peptide (Asp16→Ala), a P12 peptide (Lys12→Ala) or combination thereof. 
     
     
         4 . The anti-MSCRAMM:fibrinogen antibody of  claim 2 , wherein said peptide is a modified native MSCRAMM binding region where the peptide is a P16 peptide having a Asp to Ala mutation at 16 or a P12 peptide having a Lys to Ala mutation at 12. 
     
     
         5 . The anti-MSCRAMM:fibrinogen antibody of  claim 1 , wherein said antibody is generated using peptides derived from fibrinogen binding region of MSCRAMM, said peptide differing from the native MSCRAMM in at least one amino acid residue. 
     
     
         6 . The anti-MSCRAMM:fibrinogen antibody of  claim 1 , wherein said antibody is a monoclonal antibody, a polyclonal antibody or a chimeric antibody. 
     
     
         7 . The anti-MSCRAMM:fibrinogen antibody of  claim 1 , wherein the MSCRAMM is present on  Staphylococcus aureus, Staphylococcus lugdunensis , or  Staphylococcus epidermis.   
     
     
         8 . An anti-microbial surface components recognizing adhesive matrix molecule (anti-MSCRAMM):fibrinogen antibody effective to inhibit an microbial surface components recognizing adhesive matrix molecule (MSCRAMM) interaction with fibrinogen but does not affect binding of other proteins to fibrinogen. 
     
     
         9 . The anti-MSCRAMM:fibrinogen antibody of  claim 8 , wherein said anti-MSCRAMM:fibrinogen antibody is generated using a peptide comprising a modified native MSCRAMM binding region on Fibrinogen differing from the native MSCRAMM binding region on Fibrinogen in at least one amino acid residue. 
     
     
         10 . The anti-MSCRAMM:fibrinogen antibody of  claim 9 , wherein said modified native MSCRAMM binding region is a peptide is a P16 peptide having a Asp to Ala mutation at 16 or a P12 peptide having a Lys to Ala mutation at 12. 
     
     
         11 . The anti-MSCRAMM:fibrinogen antibody of  claim 8 , wherein said anti-MSCRAMM:fibrinogen antibody is generated using a peptide comprising a modified fibrinogen binding region of a MSCRAMM, said peptide differing from a native fibrinogen binding region of a MSCRAMM by at least one amino acid residue. 
     
     
         12 . The anti-MSCRAMM:fibrinogen antibody of  claim 8 , wherein said anti-MSCRAMM:fibrinogen antibody is a monoclonal antibody, a polyclonal antibody or a chimeric antibody. 
     
     
         13 . The anti-MSCRAMM:fibrinogen antibody of  claim 8 , wherein the MSCRAMM is present on  Staphylococcus aureus, Staphylococcus lugdunensis , or  Staphylococcus epidermis.