Method for modulating microbial quorum sensing

Abstract

The present invention provides compositions and methods for modulating bacterial quorum sensing using antagonist or agonist compounds. Further, the present invention provides methods of treating or preventing microbial damages and diseases, in particular for diseases where there is an advantage in inhibiting quorum sensing regulated phenotypes of pathogens.

1 . A method for modulating quorum sensing of a bacterium comprising contacting said bacterium with at least one quorum sensing compound selected from the group consisting of:  
     
       
         
         
             
             
         
       
     
     wherein X 1 , X 2 , X 3 , X 4 , and X 5  is selected from a group consisting of H, OH, F, Cl, Br, I, OR 1 , COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;  
     
       
         
         
             
             
         
       
     
     wherein X 1  is O, S, N; X 2  is O; Y is selected from a group consisting of a heterocyclic aromatic ring, having a nucleophilic group; an aromatic ring having a nucleophilic group; and  
     
       
         
         
             
             
         
       
     
     wherein the nucleophilic group is selected from the group consisting of OH, F, Cl, Br, I, OR, COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       2 . A method according to  claim 1 , wherein the bacterium is  Pseudomonas aeruginosa.    
   
   
       3 . A method according to  claim 1 , further comprising contacting said bacterium with a suitable antibiotic.  
   
   
       4 . A method according to  claim 3 , where said antibiotic is selected from the sting of aminoglycosides, β-lactam antibiotics, and fluoroquinolones.  
   
   
       5 . A pharmaceutical composition comprising 
 (a) a quorum sensing compound selected from the group consisting of:                          X 2 , X 3 , X 4 , and X 5  is selected from a group consisting of H, OH, F, Cl, Br, I, OR 1 , R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;                          wherein X 1  is O, S, N; X 2  is O; Y is selected from a group consisting of a heterocyclic aromatic ring, having a nucleophilic group; an aromatic ring having a nucleophilic group; and                          wherein the nucleophilic group is selected from the group consisting of OH, F, Cl, Br, I, OR, COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;                                                              (b) a pharmaceutically acceptable salt of said compound; and    (c) a pharmaceutically-acceptable carrier.    
   
   
       6 . A pharmaceutical composition according to  claim 5 , further comprising an antibiotic.  
   
   
       7 . A method for modulating biofilm formation on a surface, the method comprising administering to said surface a quorum sensing compound selected from the group consisting of:  
     
       
         
         
             
             
         
       
     
     wherein X 1 , X 2 , X 3 , X 4 , and X 5  is selected from a group consisting of H, OH, F, Cl, Br, I, OR 1 , COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;  
     
       
         
         
             
             
         
       
     
     wherein X 1  is O, S, N; X 2  is O; Y is selected from a group consisting of a heterocyclic aromatic ring, having a nucleophilic group; an aromatic ring having a nucleophilic group; and  
     
       
         
         
             
             
         
       
     
     wherein the nucleophilic group is selected from the group consisting of OH, F, Cl, Br, I, OR, COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       8 . A method of regulating microbial disease resistance or susceptibility to a microbial disease in a subject comprising the step of contacting said microbe with a quorum sensing compound selected from the group consisting of:  
     
       
         
         
             
             
         
       
     
     wherein X 1 , X 2 , X 3 , X 4 , and X 5  is selected from a group consisting of H, OH, F, Cl, Br, I, OR 1 , COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;  
     
       
         
         
             
             
         
       
       wherein X 1  is O, S, N; X 2  is O; Y is selected from a group consisting of a heterocyclic aromatic ring, having a nucleophilic group; an aromatic ring having a nucleophilic group; and  
       
         
           
           
               
               
           
         
       
       wherein the nucleophilic group is selected from the group consisting of OH, F, Cl, Br, I, OR, COOR 1  and R 1 , wherein R 1  is C n H 2n-1  and n is an integer between 0-5;