Method of treating an eye disorder by inhibiting or disrupting bacterial biofilm formation

Abstract

The present invention relates to methods of treating blepharitis and dry eye by inhibiting the binding ability of lid flora bacteria such as Staphylococcus aureus and Staphylococcus epidermidis, thus inhibiting biofilm formation and the increase in bacterial populations and densities that lead to quorum-sensing-gene activation and therefore, the production of inflammatory virulence factors.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising at least one biofilm inhibiting compound provided at a dose sufficient to disrupt a biofilm on the eyelid margin or to disperse a biofilm already formed on the eyelid margin. 
     
     
         2 . The composition of  claim 1 , wherein the at least one biofilm inhibiting compound is selected from a protein, protein fragment, an antibody, and a small molecule. 
     
     
         3 . The composition of  claim 1 , wherein the at least one biofilm inhibiting compound is an antibody or antibody fragment against a protein selected from the group consisting of Staphylococcal protein A (SpA), clumping factor A, clumping factor B, fibrinogen-binding protein SdrG, fibrinogen-binding protein SdrF, S. epidermidis Extracellular Motif Binding Protein (Embp), LPXTG motif-containing S. epidermidis surface protein SesC, S. aureus collagen-binding protein, S. aureus fibronectin-binding protein, S. aureus fibronectin-binding protein A, S. aureus fibronectin-binding protein B, Heat Shock Protein 60, staphylococcal 145 kDa cell wall adhesin, S. epidermidis AtlE, S. epidermidis Aae, S. epidermidis AtlE, S. epidermidis Aae, S. epidermidis polysaccharide intercellular adhesin, S. aureus polysaccharide intercellular adhesin, β1 integrin, and combinations thereof, and further wherein, the antibody is capable of blocking the activity of adhesin protein in biofilm formation. 
     
     
         4 . The composition of  claim 1 , wherein the at least one biofilm inhibiting compound is selected from the group consisting of cytochalasin D, genistein, SAR 1118, fibronectin, delmopinol, S. aureus Clf40 (N1 N2N3), S. aureus Clf41 (N2N3), S. epidermidis SdrG (N1 N2N3), S. epidermidis SdrG (AA 50-597), S. epidermidis SdrG (N2N3), thymosin β4, lactoferrin, xylitol, mangainin I covalently linked to II-mercapto undecanoic acid and 6-mercaptohexanol in 1:3 ratio, Fraction 7 from Terminalia chebula, FnBP-derived peptides, and combinations thereof. 
     
     
         5 . A method of inhibiting a biofilm on the eyelid margin of a subject comprising administering to the eyelid margin of the subject a dose of at least one biofilm inhibiting compound in a dose sufficient to disrupt a biofilm on the eyelid margin or to disperse a biofilm already formed on the eyelid margin. 
     
     
         6 . The method of  claim 5 , wherein the at least one biofilm inhibiting compound is selected from a protein, protein fragment, an antibody, and a small molecule. 
     
     
         7 . The method of  claim 5 , wherein the at least one biofilm inhibiting compound binds to an adhesin protein. 
     
     
         8 . The method of  claim 5 , wherein the at least one biofilm inhibiting compound binds to a receptor for an adhesin protein. 
     
     
         9 . The method of  claim 5 , wherein the at least one biofilm inhibiting compound is an antibody or antibody fragment against a protein selected from the group consisting of Staphylococcal protein A (SpA), clumping factor A, clumping factor B, fibrinogen-binding protein SdrG, fibrinogen-binding protein SdrF, S. epidermidis Extracellular Motif Binding Protein (Embp), LPXTG motif-containing S. epidermidis surface protein SesC, S. aureus collagen-binding protein, S. aureus fibronectin-binding protein, S. aureus fibronectin-binding protein A, S. aureus fibronectin-binding protein B, Heat Shock Protein 60, staphylococcal 145 kDa cell wall adhesin, S. epidermidis AtlE, S. epidermidis Aae, S. epidermidis AtlE, S. epidermidis Aae, S. epidermidis polysaccharide intercellular adhesin, S. aureus polysaccharide intercellular adhesin, β1 integrin, and combinations thereof, and further wherein, the antibody is capable of blocking the activity of adhesin protein in biofilm formation. 
     
     
         10 . The method of  claim 5 , wherein the at least one biofilm inhibiting compound is selected from the group consisting of cytochalasin D, genistein, SAR 1118, fibronectin, delmopinol, S. aureus Clf40 (N1 N2N3), S. aureus Clf41 (N2N3), S. epidermidis SdrG (N1 N2N3), S. epidermidis SdrG (AA 50-597), S. epidermidis SdrG (N2N3), thymosin β4, lactoferrin, xylitol, mangainin I covalently linked to II-mercapto undecanoic acid and 6-mercaptohexanol in 1:3 ratio, Fraction 7 from Terminalia chebula, FnBP-derived peptides, and combinations thereof.