Compositions and methods for the removal of biofilms

Abstract

Methods of breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of a polypeptide that has one or more HMG-box domains to a subject suffering from the infection or having the biofilm. By competing with microbial proteins that bind to DNA scaffold in the biofilm, these polypeptides destabilize the biofilm leading to destruction and removal of the biofilm by the immune system.

1 . A method for inhibiting, competing or titrating the binding of a DNABII polypeptide or protein to a microbial DNA, comprising contacting the DNABII polypeptide or protein or the microbial DNA with a polypeptide comprising an HMG-box domain, thereby inhibiting, competing or titrating the binding of the DNABII protein or polypeptide to the microbial DNA. 
     
     
         2 . A method for inhibiting, preventing or breaking down a microbial biofilm, comprising contacting the biofilm with a polypeptide comprising an HMG-box domain, thereby inhibiting, preventing or breaking down the microbial biofilm. 
     
     
         3 . The method of  claim 1 , wherein the contacting is in vitro or in vivo. 
     
     
         4 . A method of inhibiting, preventing or breaking down a biofilm in a subject, comprising administering to the subject an effective amount of a polypeptide comprising an HMG-box domain, thereby inhibiting, preventing or breaking down the microbial biofilm. 
     
     
         5 . A method for inhibiting, preventing or treating a microbial infection that produces a biofilm in a subject, comprising administering to the subject an effective amount of a polypeptide comprising an HMG-box domain, thereby inhibiting, preventing or treating a microbial infection that produces the biofilm in the subject. 
     
     
         6 . The method of  claim 1 , wherein the polypeptide comprising an HMG-box domain comprises one or more of:
 (a) an isolated or recombinant protein HMGB1 or a fragment thereof that comprises one or more HMG-box domains;   (b) an isolated or recombinant protein HMGB2 or a fragment thereof that comprises one or more HMG-box domains;   (c) an isolated or recombinant protein HMGB3 or a fragment thereof that comprises one or more HMG-box domains;   (d) an isolated or recombinant protein HMGB4 or a fragment thereof that comprises one or more HMG-box domains; or   (e) a polypeptide that is at least about 70% identical to any of (a), (b), (c) or (d).   
     
     
         7 . The method of  claim 1 , wherein the polypeptide comprising an HMG-box domain comprises an isolated or recombinant protein HMGB1, a polypeptide that is at least about 70% identical to HMGB1, or a fragment thereof that comprises one or more HMG-box domains. 
     
     
         8 . The method of  claim 6 , wherein the isolated or recombinant protein is selected from the group of: a mammalian protein that is or is not post-translationally modified, a mammalian protein that is or is not post-translationally alkylated or a protein expressed in a non-mammalian system. 
     
     
         9 . The method of  claim 8 , wherein the mammalian protein is a human protein. 
     
     
         10 . The method of  claim 4 , further comprising administering to the subject an effective amount of one or more of an antimicrobial, an antigenic peptide or an adjuvant. 
     
     
         11 . The method of  claim 4 , wherein the subject is a non-human animal or a human patient. 
     
     
         12 . The method of  claim 4 , wherein the polypeptide is administered by a method comprising topically, transdermally, sublingually, rectally, vaginally, ocularly, subcutaneous, intramuscularly, intraperitoneally, urethrally, intranasally, by inhalation or orally. 
     
     
         13 . The method of  claim 4 , wherein the subject is a pediatric patient and the polypeptide is administered in a formulation for the pediatric patient. 
     
     
         14 . The method of  claim 4 , wherein the biofilm comprises microbial DNA from a microorganism identified in Table 1. 
     
     
         15 . The method of  claim 4 , wherein the polypeptide is administered locally to the microbial infection. 
     
     
         16 . A method for inducing or providing an immune response in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide comprising an HMG-box domain. 
     
     
         17 . The method of  claim 16 , wherein the administration is local to where the immune response is desired. 
     
     
         18 . The method of  claim 16 , wherein the polypeptide comprising an HMG-box domain comprises one or more of:
 (a) an isolated or recombinant protein HMGB1 or a fragment thereof that comprises one or more HMG-box domains;   (b) an isolated or recombinant protein HMGB2 or a fragment thereof that comprises one or more HMG-box domains;   (c) an isolated or recombinant protein HMGB3 or a fragment thereof that comprises one or more HMG-box domains;   (d) an isolated or recombinant protein HMGB4 or a fragment thereof that comprises one or more HMG-box domains; or   (e) a polypeptide that is at least about 70% identical to any of (a), (b), (c) or (d).   
     
     
         19 . The method of  claim 16 , wherein the polypeptide comprising an HMG-box domain comprises an isolated or recombinant protein HMGB1, a polypeptide that is at least about 70% identical to HMGB1, or a fragment thereof that comprises one or more HMG-box domains. 
     
     
         20 . The method of  claim 18 , wherein the isolated or recombinant protein is a mammalian protein. 
     
     
         21 . The method of  claim 20 , wherein the mammalian protein is a human protein. 
     
     
         22 . The method of  claim 16 , wherein the subject is a non-human animal or a human patient.