Targeted enzymatic degradation of quorum-sensing peptides
Methods and compositions for the treatment of biofilms and/or the inhibition of biofilm formation. In one embodiment, a biofilm is treated and/or biofilm formation is inhibited by a method comprising contacting a biofilm or a surface with a bifunctional ligand comprising a quorum-sensing-peptide-binding region and a protease-binding region, whereby the biofilm is treated and/or biofilm formation on the surface is inhibited.
1. A method for treating a biofilm and/or inhibiting biofilm formation, comprising:
positioning a surface of a carrier material adjacent to a surface having a biofilm, the carrier material having a bifunctional ligand comprising a quorum-sensing-molecule-binding region chemically linked to a protease-binding region configured to bind a protease capable of hydrolyzing a quorum-sensing-molecule of the quorum-sensing-molecule-binding region;
positioning a sealing member over the carrier material and the surface to create a sealed environment;
fluidly coupling a reduced-pressure source to the sealed environment;
delivering reduced pressure to the surface;
binding acylated homoserine lactones (AHLs) with the quorum-sensing-molecule; and
binding a lactonase with the protease-binding region.
2. The method of claim 1 , wherein the biofilm comprises Gram-positive bacteria.
3. The method of claim 2 , wherein the Gram-positive bacteria is one or more of Staphylococcus aureus, Staphylococcus epidermis, Streptococcus pyogenes (group A), Streptococcus species (viridans group), Streptococcus agalactiae (group B), Streptococcus bovis, Streptococcus pneumoniae, Enterococcus species, Bacillus anthracis, Corynebacterium diphtheriae, Listeria monocytogenes, Clostridium tetani , or Clostridium difficile.
4. The method of claim 1 , wherein the biofilm comprises Gram-negative bacteria.
5. The method of claim 4 , wherein the Gram-negative bacteria is one or more of Escherichia coli, Enterobacter species, Proteus mirablis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella species, Shigella species, Serratia species, Campylobacter species, Neisseria species, or Branhamella catarrhalis.
6. The method of claim 1 , wherein the biofilm comprises a dermatophyte.
7. The method of claim 6 , wherein the dermatophyte is one or more of Microsporum canis, Trichophyton rubrum , and/or Trichophyton mentagrophytes.
8. The method of claim 1 , wherein the biofilm comprises a yeast.
9. The method of claim 8 , wherein the yeast is one or more of Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, Epidermophyton floccosum, Malassezia furfur, Pityropsporon orbiculare, Pityropsporon ovale, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus species, Zygomycetes species, Rhizopus species, Mucor species, Fusarium species, Paracoccidioides brasiliensis, Blastomyces dermatitides, Histoplasma capsulatum, Coccidioides immitis , and/or Sporothrix schenckii.
10. The method of claim 1 , wherein the surface is a tissue site.
11. The method of claim 10 , wherein the tissue site is in contact with an indwelling medical device.
12. The method of claim 1 , wherein the surface is an indwelling medical device.
13. The method of claim 12 , wherein the indwelling medical device is a catheter or a ventilation tube.
14. The method of claim 1 , further comprising contacting the surface with an antibiotic.
15. The method of claim 1 , wherein the quorum-sensing-molecule-binding region and the protease-binding region are chemically linked with a linker comprising a peptide of about 1 to about 50 amino acids in length.