Controlling biofilms with cyclopropanated fatty acids

Abstract

Compositions and methods for using cyclopropanated structural analogs of fatty acid biofilm dispersal agents are characterized by superior biofilm dispersion. When used in combination with antimicrobials, these analogs decrease the minimum inhibitory concentration of antimicrobial agents required for eradication of the biofilm and/or treatment of infection. Methods for using these analogs include direct application to a surface, blending with lipid based carriers, or covalent anchoring the molecule to a surface. Typically, the cyclopropanated structural analog has the structure according to formula (I): wherein R 1 is a C 1 -C 24 linear or branched alkyl group; or an acid halide or acid anhydride thereof.

1 . A biofilm removing and/or inhibiting composition comprising one or more compounds derived from a mono-unsaturated fatty acid, wherein said compound is cyclopropanated at the double bond of said fatty acid, and wherein said fatty acid is effective to remove or disrupt a bacterial biofilm or inhibit normal biofilm formation. 
     
     
         2 . The biofilm removing and/or inhibiting composition according to  claim 1 , wherein said fatty acid is a cis fatty acid. 
     
     
         3 . The biofilm removing and/or inhibiting composition according to  claim 1 , wherein said fatty acid has a terminal carboxylic acid. 
     
     
         4 . The biofilm removing and/or inhibiting composition according to  claim 1 , wherein said compound has the structure according to formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is a C 1 -C 24  linear or branched alkyl group; 
         or acid halides and acid anhydrides thereof. 
       
     
     
         5 . The biofilm removing and/or inhibiting composition according to  claim 4 , wherein said compound has the structure according to formula (Ia) and/or (Ib): 
       
         
           
           
               
               
           
         
       
     
     
         6 . The biofilm removing and/or inhibiting composition according to  claim 4 , wherein R 1  is unsubstituted. 
     
     
         7 . The biofilm removing and/or inhibiting composition according to  claim 4 , wherein R 1  is a linear alkyl. 
     
     
         8 . The biofilm removing and/or inhibiting composition according to  claim 1  wherein said compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The biofilm removing and/or inhibiting composition according to  claim 1  further comprising an additive component selected from biocides, surfactants, antibiotics, antiseptics, detergents, chelating agents, virulence factor inhibitors, pharmaceutically acceptable carriers, excipients, or combinations thereof. 
     
     
         10 . The biofilm removing and/or inhibiting composition according to  claim 1 , wherein said composition comprises an amount of said compound effective to remove or disrupt a bacterial biofilm or inhibit normal biofilm formation. 
     
     
         11 . The biofilm removing and/or inhibiting composition according to  claim 1 , wherein said composition is mouthwash or dentifrice. 
     
     
         12 . The biofilm removing and/or inhibiting composition according to  claim 1 , wherein said composition is a pharmaceutical composition further comprising one or more pharmaceutically acceptable carriers or excipients. 
     
     
         13 . The biofilm removing and/or inhibiting composition according to  claim 12 , wherein said composition further comprises an antibiotic. 
     
     
         14 . The biofilm removing and/or inhibiting composition according to  claim 13 , wherein said antibiotic is tobramycin, tetracycline, or levofloxacin. 
     
     
         15 . A method of preventing biofilm formation on a surface comprising administering an effective amount of the composition according to  claim 1  to said surface. 
     
     
         16 . The method according to  claim 15 , wherein said surface is on a medical device, an industrial water system, a marine vehicle, or a reaction vessel. 
     
     
         17 . The method according to  claim 15 , wherein said surface is on the surface of a drainpipe, a contact lens, dentures, a glaze ceramic, porcelain, glass, metal, wood, chrome, plastic, vinyl, or Formica. 
     
     
         18 . The method according to  claim 15  wherein said surface is the surface of teeth, skin, or bone. 
     
     
         19 - 37 . (canceled)