Methods and Compositions for the Disruption of Biofilms

Abstract

The invention relates to methods of inhibiting biofilm formation or reducing biofilms in a subject or on a device or surface by administering a charged compound such as a polyamino acid to a subject, device or surface. The invention also relates to compositions for inhibiting biofilm formation or reducing biofilms.

1 . (canceled) 
     
     
         2 . The method of  claim 52 , wherein the compound is a polyamino acid. 
     
     
         3 . The method of  claim 2 , wherein the polyamino acid comprises both charged and neutral amino acids. 
     
     
         4 . The method of  claim 2 , wherein the polyamino acid is anionic. 
     
     
         5 . The method of  claim 4 , wherein the polyamino acid is polyaspartic acid or polyglutamic acid. 
     
     
         6 . The method of  claim 2 , wherein the polyamino acid is cationic. 
     
     
         7 . The method of  claim 6 , wherein the polyamino acid is polyarginine, polylysine or polyhistidine. 
     
     
         8 . The method of  claim 2 , wherein the polyamino acid is between 50 and 300 amino acids in length. 
     
     
         9 . The method of  claim 52 , further comprising administering to the subject a protease inhibitor. 
     
     
         10 . The method of  claim 52 , further comprising administering to the subject an anti-DNA compound. 
     
     
         11 . The method of  claim 52 , further comprising administering to a subject a compound that inhibits accumulation of, inhibits necrosis of, or inhibits release of the cellular contents of, cells that undergo necrosis, at or proximal to the site of biofilm formation or the site of infection by a microorganism that forms biofilms. 
     
     
         12 . The method of  claim 11 , wherein the cells that undergo necrosis are neutrophils. 
     
     
         13 . The method of  claim 12  wherein the compound inhibits the adherence of, migration to, or the sensing or response to chemoattractants by neutrophils, or inhibits the activity or release of a cytokine, chemokine or chemoattractant that attracts or enhances neutrophil activity. 
     
     
         14 . The method of  claim 13 , wherein the compound is an anti-inflammatory compound. 
     
     
         15 . The method of  claim 11 , further comprising administering to the subject an anti-DNA compound. 
     
     
         16 . The method of  claim 52 , further comprising administering to the subject an anti-mucin compound. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 52 , wherein the compound is administered when cystic fibrosis, bacterial keratitis or an infection associated with a severe burn or wound is diagnosed or suspected. 
     
     
         19 . The method of  claim 52 , wherein the compound is administered prior to the treatment of the subject with a process that may cause a biofilm to form in the patient. 
     
     
         20 . The method of  claim 52 , wherein the compound is administered with a pharmaceutically acceptable carrier. 
     
     
         21 . The method of  claim 52 , wherein the compound is administered directly to or proximal to the site of biofilm formation or potential therefore. 
     
     
         22 . The method of  claim 52 , wherein the compound is administered to the lung or airways of the subject. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 52 , wherein the compound is applied to the site of a wound or to the wound dressing when the wound is treated. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 52 , wherein the biofilm forms in connection with cystic fibrosis or bacterial keratitis in an organ, tissue or body system. 
     
     
         28 . The method of  claim 52 , wherein the biofilm forms on a surface of a tissue, organ or bodily part. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 11 , wherein the microorganism is  Pseudomonas aeruginosa.   
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . The method of  claim 52 , wherein the charged compound is administered to the subject prior to the development of the biofilm. 
     
     
         49 . The method of  claim 52 , wherein the charged compound is a synthetic polymer. 
     
     
         50 . The method of  claim 52 , wherein the charged compound is a polynucleotide. 
     
     
         51 . The method of  claim 52 , wherein the charged compound is a peptide nucleic acid. 
     
     
         52 . A method of treating or preventing cystic fibrosis, bacterial keratitis or an infection associated with a severe burn or wound in a subject, comprising administering to a subject a charged compound, wherein the charge compound inhibits or reduces biofilm formation associated with cystic fibrosis, bacterial keratitis or associated with an infection associated with a severe burn or wound. 
     
     
         53 . (canceled)