Compositions and method for destabilizing, altering, and dispersing biofilms

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).

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)