Compositions and methods for disrupting biofilm formation and maintenance

Patent metadata

Field	Value
Publication number	US-11541105-B2
Application number	US-201916428560-A
Country	US
Kind code	B2
Filing date	May 31, 2019
Priority date	Jun 1, 2018
Publication date	Jan 3, 2023
Grant date	Jan 3, 2023

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.

First claim

What is claimed is:

1. A method of inducing a dispersion of sessile organisms within a biofilm in an aqueous medium, comprising:
enzymatically depleting pyruvate in the aqueous medium by supplying at least 5 mU/ml of an enzyme having a pyruvate substrate specificity, to a sufficient amount and for a sufficient time to induce hypoxic stress and a resulting dispersion response of the sessile organisms within the biofilm.

2. The method according to claim 1 , wherein the enzymatically altering comprises decarboxylation.

3. The method according to claim 1 , wherein the enzymatically altering comprises phosphorylation.

4. The method according to claim 1 , further comprising adding at least cis-2-decenoic acid.

5. The method according to claim 1 , further comprising adding at least nitric oxide.

6. The method according to claim 1 , wherein the depleting comprises absorbing pyruvate to an insoluble matrix.

7. The method according to claim 1 , wherein the depleting comprises chemically transforming the pyruvate to another chemical species.

8. The method according to claim 1 , wherein the depleting comprises an imine-forming reaction.

9. The method according to claim 1 , wherein the depleting comprises operation of pyruvate decarboxylase.

10. The method according to claim 1 , wherein the depleting comprises use of a bioreactor comprising pyruvate fermentative organisms.

11. The method according to claim 1 , wherein the depleting comprises selectively administering an enzyme preparation selected from the group consisting of pyruvate dehydrogenase; pyruvate oxidase; lactate dehydrogenase; and a transaminase.

12. The method according to claim 1 , further comprising administering an antibiotic to the biofilm.

13. A method of treating a biofilm, comprising administering a formulation comprising an enzyme having a pyruvate substrate specificity to the biofilm at a level of at least 5 mU/ml, the enzyme being at least one of encapsulated and immobilized, under conditions effective for reducing pyruvate in an environment surrounding the biofilm, and causing a sufficient hypoxic stress of the cells associated with the biofilm to induce a dispersion response.

14. The method according to claim 13 , further comprising administering a bacterial biofilm dispersion inducer to a subject having the biofilm.

15. The method according to claim 13 , further comprising administering an antibiotic to the biofilm, wherein an antibacterial activity of the antibiotic is enhanced by the dispersion response.

16. The method according to claim 13 , wherein the enzyme having the pyruvate specificity is pyruvate dehydrogenase, is stabilized with respect to a soluble form of pyruvate dehydrogenase by encapsulation.

17. The method according to claim 16 , wherein the encapsulation comprises encapsulating the pyruvate dehydrogenase in chitosan nanoparticles.

18. A method of inducing a dispersion of sessile bacteria in a biofilm, comprising:
enzymatically depleting pyruvate in an aqueous medium surrounding the biofilm, to induce hypoxic stress in the sessile bacteria and resulting is a dispersion response of the sessile organisms, with an enzyme that is encapsulated, which is stabilized with respect to a corresponding soluble form of the enzyme by the encapsulation to retain at least 50% of its initial activity for 48 hrs after hydration at 37° C. to a concentration of at least 5 mU/ml.

Assignees

• Univ New York State Res Found

Inventors

• Sauer Karin
• Doiron Amber L

Classifications

• C12R2001/38

  Pseudomonas · CPC title

• A61K38/44 Primary

  Oxidoreductases (1) · CPC title

• C12R2001/185

  Escherichia · CPC title

• C12N1/00

  Microorganisms; Compositions thereof (medicinal preparations containing material from protozoa, bacteria or viruses A61K35/66, from algae A61K36/02, from fungi A61K36/06; preparing medicinal bacterial antigen or antibody compositions, e.g. bacterial vaccines, A61K39/00); Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor · CPC title

• A61K31/7036

  having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins · CPC title