Quorum sensing and biofilm formation

Abstract

The present invention is based on the discovery that interspecies quorum sensing is related to biofilm formation. The present invention provides methods useful for treating or preventing biofilm formation and microbial infections associated with biofilm formation by using an agent that either increases LuxS-dependent pathway or interspecies quorum sensing signal. The present invention also provides compositions containing an anti-micorbial agent and an agent that either increases LuxS-dependent pathway or interspecies quorum sensing signal.

1 . A composition comprising an anti-microbial agent and an agent that increases LuxS-dependent signal pathway in a bacterium.  
     
     
         2 . A composition comprising an anti-microbial agent and an agent that increases an interspecies quorum sensing signal.  
     
     
         3 . The composition of  claim 1 , wherein the agent increases an interspecies quorum sensing signal.  
     
     
         4 . The composition of  claim 1 , wherein the agent is an interspecies quorum sensing signal.  
     
     
         5 . The composition of  claim 1 , wherein the agent is autoinducer-2.  
     
     
         6 . The composition of  claim 1 , wherein the agent is LuxS.  
     
     
         7 . The composition of  claim 1 , wherein the agent increases the activity of LuxS in interspecies quorum sensing.  
     
     
         8 . The composition of  claim 1 , wherein the anti-microbial agent is an antibiotic.  
     
     
         9 . The composition of  claim 8 , wherein the antibiotic is selected from the group consisting of penicillin, quinoline, vancomycin, and sulfonamide.  
     
     
         10 . The composition of  claim 8 , wherein the antibiotic is selected from the group consisting of ampicillin, ciprofloxacin, and sulfisoxazole.  
     
     
         11 . The composition of  claim 8 , wherein the anti-microbial agent comprising a targeting moiety and an anti-microbial peptide moiety, wherein the targeting moiety is coupled to the anti-microbial peptide moiety and recognizes a target microbial organism and wherein the composition has an anti-microbial effect on a target microbial organism.  
     
     
         12 . The composition of  claim 8  further comprising a pharmaceutically acceptable carrier.  
     
     
         13 . A method of treating a disease condition associated with bacterial biofilm formation comprising administering to a subject in need of such treatment the composition of  claim 1 .  
     
     
         14 . The method of  claim 13 , wherein the disease condition is on an epithelial or a mucosal surface.  
     
     
         15 . The method of  claim 14 , wherein the mucosal surface is selected from the group consisting of mouth, vagina, gastrointestinal tract, and esophageal tract.  
     
     
         16 . The method of  claim 13 , wherein the disease condition is an oral infection.  
     
     
         17 . The method of  claim 13 , wherein the disease condition is caused by  S. mutans.    
     
     
         18 . A method of treating a microbial infection associated with biofilm formation comprising administering to a population of bacteria an anti-microbial agent and an agent that increases LuxS-dependent signal pathway in a bacterium.  
     
     
         19 . A method of treating microbial infection associated with biofilm formation comprising administering to a population of bacteria an anti-microbial agent and an agent that increases interspecies quorum sensing signal.  
     
     
         20 . A method of treating bacterial biofilm formation on a surface comprising contacting the surface with an anti-microbial agent and an agent that increases LuxS-dependent signal pathway in a bacterium.  
     
     
         21 . A method of treating bacterial biofilm formation on a surface comprising contacting the surface with an anti-microbial agent and an agent that increases interspecies quorum sensing signal.  
     
     
         22 . A method of preventing or inhibiting bacteria biofilm formation or sensitizing bacteria for an anti-bacteria treatment comprising administering an agent to a population of bacteria, wherein the agent increases LuxS-dependent signal pathway in a bacterium.  
     
     
         23 . A method of preventing or inhibiting bacteria biofilm formation or sensitizing bacteria for an anti-bacteria treatment comprising administering an agent to a population of bacteria, wherein the agent increases interspecies quorum sensing signal.