Targeted enzymatic degradation of quorum-sensing peptides
View Patent ↗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 bifunctional ligand, comprising:
a quorum-sensing-molecule-binding region adapted to bind one or more of an acylated homoserine lactone (AHL), an autoinducing peptide (AIP), AI-2 (a furanosyl borate diester), a γ-butyrolactone, and a competence stimulating peptide (CSP); and
a protease-binding region chemically linked to the quorum-sensing-molecule-binding region, wherein the protease-binding region is adapted to bind a lactonase.
2. The bifunctional ligand of claim 1 , wherein the quorum-sensing-molecule-binding region comprises a quorum-sensing molecule receptor or a quorum-sensing molecule receptor fragment.
3. The bifunctional ligand of claim 1 , wherein the quorum-sensing-molecule-binding region comprises an antibody or an antibody fragment that binds a quorum-sensing molecule.
4. The bifunctional ligand of claim 1 , further comprising a peptide linker between the quorum-sensing-molecule-binding region and the protease-binding region.
5. A composition comprising a bifunctional ligand of claim 1 and a pharmaceutically acceptable carrier.
6. The composition of claim 5 , wherein the composition is formulated as a liquid, gel, or foam.
7. The composition of claim 5 , wherein the composition further comprises an antibiotic.
8. The composition of claim 5 , wherein the composition further comprises a protease.
9. A kit comprising the composition of claim 5 .
10. The kit of claim 9 , further comprising an antibiotic.
11. The kit of claim 9 , further comprising a protease.
12. A dressing for treating a wound, comprising:
a distribution manifold comprising an open-cell foam; and
a bifunctional ligand disposed on a surface of the distribution manifold and comprising a quorum-sensing-molecule-binding region chemically linked to a protease-binding region.
13. The dressing of claim 12 , further comprising a sealing member adapted to be positioned over the distribution manifold and the wound to create a sealed environment.
14. The dressing of claim 13 , further comprising a reduced-pressure source adapted to be in fluid communication with the sealed environment.
15. A system for treating a tissue site, comprising:
a distribution manifold adapted to be placed over the tissue site;
a sealing member for covering the distribution manifold and for creating a sealed environment around the tissue site;
a reduced-pressure source adapted to be in fluid communication with the sealed environment; and
a fluid-delivery source adapted to supply a solution comprising a bifunctional ligand comprising a quorum-sensing-molecule-binding region chemically linked to a protease-binding region.
16. The system of claim 15 , wherein the distribution manifold comprises a non-woven fabric material.
17. The system of claim 15 , wherein the distribution manifold comprises a woven fabric material.