Eradication of bacterial biofilm using anti-amyloid monoclonal antibodies
The present invention features compositions comprising an anti-amyloid antibody and methods of treating microbial infection and treating or preventing microbial biofilms using the composition.
1. A composition comprising a therapeutic antibody, wherein the antibody is specific for binding to an epitope of curli and further wherein the epitope of curli comprises a sequence having homology to an antibody binding site of one or more heterologous amyloid proteins;
wherein the antibody is a monoclonal antibody selected from the group consisting of:
a) ALZ.3H3, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:2 and at least one light chain amino acid sequence as set forth in SEQ ID NO:35;
b) ALZ.4G1, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:61 and at least one light chain amino acid sequence as set forth in SEQ ID NO:63; and
c) ALZ.4A6, comprising at least one of a heavy chain amino acid sequence as set forth in SEQ ID NO:57 and at least one light chain amino acid sequence as set forth in SEQ ID NO:59.
2. The composition of claim 1 , wherein the antibody inhibits fibrillization of one or more heterologous amyloid proteins.
3. The composition of claim 1 , wherein the antibody prevents biofilm formation or alters biofilm architecture.
4. The composition of claim 1 , wherein the antibody is effective in reducing biofilm mass.
5. The composition of claim 3 , wherein the biofilm mass is associated with a bacteria selected from the group consisting of gram-positive, gram-negative, and a combination thereof.
6. The composition of claim 1 , wherein the antibody inhibits amyloid-β fibrillization and prevents biofilm formation or alters biofilm architecture.
7. The composition of claim 1 , wherein the antibody is a monoclonal antibody selected from the group consisting of:
a) ALZ.3H3, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:2 and at least one light chain amino acid sequence as set forth in SEQ ID NO:35; and
b) ALZ.4G1, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:61 and at least one light chain amino acid sequence as set forth in SEQ ID NO:63.
8. The composition of claim 1 , wherein the composition is for application to a surface of a medical device.
9. The composition of claim 1 , further comprising an antibiotic.
10. The composition of claim 1 , further comprising one or more pharmaceutically acceptable carriers or excipients.
11. The composition of claim 1 , wherein the formulation is a topical formulation in the form of a cream, a lotion, an ointment, a hydrogel, a colloid, a gel, a foam, an oil, a milk, a suspension, a wipe, a sponge, a solution, an emulsion, a paste, a patch, a pledget, a swab, a dressing, a spray or a pad.
12. A method of decolonizing a microbial organism comprising contacting the microbial organism with a composition according to claim 1 .
13. A method of destroying or disrupting or inhibiting or reducing biofilm formation of a microbial organism comprising contacting the microbial organism with a composition according to claim 1 .
14. The method of claim 11 , wherein the microbial organism is a bacterium.
15. A method of treating a microbial infection in a subject comprising administering to the subject a therapeutically effective amount of the composition of claim 1 .
16. The method of claim 15 , wherein the microbial infection is a bacterial infection.
17. The method of claim 16 , wherein the bacterial infection is characterized by colonization of a bacterium.
18. The method of claim 17 , wherein the bacterial infection is characterized by biofilm formation.
19. The method of claim 15 , wherein the microbial infection is a topical infection.
20. The method of claim 19 , wherein the topical infection is selected from wound, ulcer and lesion.