Compositions and method for destabilizing, altering, and dispersing biofilms

Patent metadata

Field	Value
Publication number	US-2016235698-A1
Application number	US-201415023111-A
Country	US
Kind code	A1
Filing date	Sep 24, 2014
Priority date	Sep 24, 2013
Publication date	Aug 18, 2016
Grant date	—

Abstract

The present disclosure relates to compositions and methods for destabilizing biofilms, altering biofilm 3D structure, and dispersing biofilms, in order to enhance biofilm cell removal and/or sensitivity to other agents (e.g., environmental or co-applied treatments). In particular, the present disclosure relates to the use of L-arginine in the removal and/or sensitization (e.g., to antimicrobials) of microorganisms in medical, industrial, domestic, or environmental applications, as well as treatment of bacterial infections (e.g., in biofilms).

First claim

1 . A method of inducing cell-damage, killing cells, disrupting intra-cellular processes leading to deregulation/loss of homeostasis, disrupting cell-cell adhesion, inducing three dimensional rearrangement of architecture, disrupting cell-cell signaling, disrupting cell-cell metabolic interactions, disrupting adhesion to surfaces, reducing the pathogenic potential of biofilms, reducing biofilm mass, decreasing the proportion of pathogenic bacteria in a biofilm, increasing the proportion of beneficial bacteria in a biofilm, and/or preventing growth of a microorganism in a biofilm, comprising:
contacting bacteria in a biofilm with cell-free L-arginine at a concentration of at least 1 mM, wherein said contacting results in one or more of: inducing cell-damage, killing cells, disrupting intra-cellular processes leading to deregulation/loss of homeostasis, disrupting cell-cell adhesion, inducing three dimensional rearrangement of architecture, disrupting cell-cell signaling, disrupting cell-cell metabolic interactions, disrupting adhesion to surfaces, reducing the pathogenic potential of biofilms, increasing the proportion of beneficial bacteria in a biofilm, and preventing growth of said microorganism.

2 . The method of claim 1 , wherein said microorganism is a bacteria.

3 . The method of claim 2 , wherein said bacteria are in a coaggregate.

4 . The method of claim 1 , wherein said biofilm is a dental biofilm.

5 . The method of claim 2 , wherein said bacteria are in a coaggregate or biofilm with a plurality of different bacterial species.

6 . The method of claim 1 , wherein said L-arginine prevents coaggregation or de-adhesion/dispersion of said bacteria.

7 . The method of claim 1 , wherein said L-arginine is present at a concentration of at least 100 mM.

8 . The method of claim 1 , wherein said L-arginine is present at a concentration of at least 200 mM.

9 . The method of claim 1 , wherein said L-arginine is present at a concentration of at least 500 mM.

10 . The method of claim 5 , wherein said bacterial species are Streptococci spp. and Actinomyces spp.

11 . The method of claim 10 , wherein said bacterial species are S. gordonii and A. oris.

12 . The method of claim 1 , further comprising contacting said bacteria with cetylpyridinium chloride (CPC).

13 . The method of claim 1 , wherein said biofilm is in saliva and said L-arginine disrupts said biofilm without antimicrobial activity.

14 - 26 . (canceled)

27 . A method of inducing cell-damage, killing cells, disrupting intra-cellular processes leading to deregulation/loss of homeostasis, disrupting cell-cell adhesion, inducing three dimensional rearrangement of architecture, disrupting cell-cell signaling, disrupting cell-cell metabolic interactions, disrupting adhesion to surfaces, reducing the pathogenic potential of biofilms, reducing biofilm mass, decreasing the proportion of pathogenic bacteria in a biofilm, increasing the proportion of beneficial bacteria in a biofilm, and/or preventing growth of a microorganism in a biofilm, comprising:
contacting bacteria in a biofilm with cell-free L-arginine at a concentration of at least 1 mM in combination with CPC, wherein said contacting results in one or more of: inducing cell-damage, killing cells, disrupting intra-cellular processes leading to deregulation/loss of homeostasis, disrupting cell-cell adhesion, inducing three dimensional rearrangement of architecture, disrupting cell-cell signaling, disrupting cell-cell metabolic interactions, disrupting adhesion to surfaces, reducing the pathogenic potential of biofilms, increasing the proportion of beneficial bacteria in a biofilm, and preventing growth of said microorganism.

28 - 47 . (canceled)

Assignees

• Univ Michigan Regents
• Univ Newcastle

Inventors

• Rickard Alexander
• Jakubovics Nick
• Samarian Derek S
• Kolderman Ethan

Classifications

• A61K31/198 Primary

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title

• A61Q11/00

  Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses · CPC title

• C12N15/746 Primary

  for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus) · CPC title

• A61K8/4926

  having six membered rings · CPC title

• G01N2500/10

  involving cells · CPC title