Compositions and methods for disrupting biofilm formation and maintenance

Abstract

A method of treating a biofilm on a surface, comprising: providing a surface having a biofilm; and administering to the surface a treatment that reduces a concentration of pyruvate of the biofilm, comprising pyruvate produced by at least a portion the biofilm, under conditions effective reducing maintenance of the biofilm on the surface. A composition, comprising purified enzyme, within a particle, effective for reducing pyruvate concentration in an aqueous suspension of the composition.

1 . A composition for inducing a dispersion of sessile organisms within a biofilm in an aqueous medium, comprising an enzyme adapted to deplete pyruvate in the aqueous medium, within an extended release reservoir or extended release formulation, configured to release the enzyme over a sufficient duration to induce hypoxic stress and a result a dispersion response of the sessile organisms within the biofilm. 
     
     
         2 . The composition according to  claim 1 , wherein the depletion comprises enzymatically altering the pyruvate by addition of a purified enzyme to the aqueous medium. 
     
     
         3 . The composition according to  claim 2 , wherein the enzymatically altering comprises decarboxylation. 
     
     
         4 . The composition according to  claim 2 , wherein the enzymatically altering comprises phosphorylation. 
     
     
         5 . The composition according to  claim 1 , further comprising cis-2-decenoic acid. 
     
     
         6 . The composition according to  claim 1 , further comprising nitric oxide. 
     
     
         7 . The composition according to  claim 1 , further comprising an insoluble matrix configured to absorb pyruvate. 
     
     
         8 . The composition according to  claim 1 , wherein the depletion comprises chemically transforming the pyruvate to another chemical species. 
     
     
         9 . The composition according to  claim 1 , wherein the depletion comprises an imine-forming reaction. 
     
     
         10 . The composition according to  claim 1 , wherein the enzyme comprises pyruvate decarboxylase. 
     
     
         11 . The composition according to  claim 1 , wherein the composition comprises a pyruvate fermentative organism which produces the enzyme. 
     
     
         12 . The composition according to  claim 1 , wherein the enzyme is selected from the group consisting of purified pyruvate dehydrogenase; purified pyruvate oxidase; purified lactate dehydrogenase; and a purified transaminase. 
     
     
         13 . The composition according to  claim 1 , further comprising an antibiotic biofilm. 
     
     
         14 . A method of treating a biofilm, comprising administering to a subject having a biofilm-associated infection, a formulation comprising a stabilized enzyme having a pyruvate substrate specificity, under conditions effective for reducing environmental pyruvate and causing a sufficient hypoxic stress of cells associated with the biofilm-associated infection to induce a dispersion response. 
     
     
         15 . The method according to  claim 14 , further comprising administering a bacterial biofilm dispersion inducer to the subject. 
     
     
         16 . The method according to  claim 14 , further comprising administering an antibiotic to the subject, wherein an antibacterial activity of the antibiotic is enhanced by the dispersion response. 
     
     
         17 . The method according to  claim 14 , wherein the biofilm-associated infection is associated with at least one of a burn, dental plaque, dental caries, gingival disease, an oral infection, a lung infection, and acne. 
     
     
         18 . The method according to  claim 14 , wherein said administering is carried out with at least one of a lotion, cream, ointment, gel, an inhaler, and a nebulizer. 
     
     
         19 . A composition, comprising a stabilized enzyme which retains at least 50% of its initial activity for 48 hrs after hydration at 37° C. to a concentration of at least 1 mU/ml, effective for reducing pyruvate concentration in an aqueous solution to exert a hypoxic stress on sessile organisms in a biofilm exposed to the aqueous solution. 
     
     
         20 . The composition according to  claim 19 , further comprising at least one of cis-2-decenoic acid, an antibiotic, and a source of nitric oxide, wherein the stabilized enzyme comprises at least one of a purified pyruvate decarboxylase, purified pyruvate dehydrogenase; purified pyruvate oxidase; purified lactate dehydrogenase; and a purified transaminase.