Compositions and methods for the removal of biofilms
View Patent ↗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 or preventing the binding of a deoxyribonucleic acid B II (DNABII) polypeptide to a microbial DNA in a biofilm present on the surface ex vivo, comprising contacting the microbial DNA in the biofilm with an amount of an isolated or recombinant polypeptide, the amount effective to inhibit or prevent the biofilm, the polypeptide comprising a high mobility group-box domain (HMG-box domain), thereby inhibiting or preventing the binding of the DNABII polypeptide to the microbial DNA.
2. The method of claim 1 , wherein the isolated or recombinant polypeptide comprising the HMG-box domain comprises one or more of:
(a) an isolated or recombinant polypeptide high mobility group box 1 (HMGB1) comprising from about amino acid 6 to about amino acid 76 or from about amino acid 90 to about amino acid 138 of SEQ ID NO: 1 or a polypeptide having at least 98% sequence identity to each thereof;
(b) an isolated or recombinant polypeptide high mobility group box 2 (HMGB2) comprising from about amino acid 9 to about amino acid 76 or from about amino acid 95 to about amino acid 160 of SEQ ID NO: 2 or a polypeptide having at least 98% sequence identity to each thereof;
(c) an isolated or recombinant polypeptide high mobility group box 3 (HMGB3) comprising from about amino acid 9 to about amino acid 75 or from about amino acid 98 to about amino acid 158 of SEQ ID NO: 3 or a polypeptide having at least 98% sequence identity to each thereof; or
(d) an isolated or recombinant polypeptide high mobility group box 4 (HMGB 4) comprising from about amino acid 9 to about amino acid 75 or from about amino acid 93 to about amino acid 158 of SEQ ID NO: 4 or a polypeptide having at least 98% sequence identity to each thereof.
3. The method of claim 2 , wherein the isolated or recombinant polypeptide comprising an HMG-box (high mobility group-box) domain comprises one or more of:
(a) a polypeptide having at least 99% sequence identity to a polypeptide from about amino acid 6 to about amino acid 76 or from about amino acid 90 to about amino acid 138 of SEQ ID NO: 1;
(b) a polypeptide having at least 99% sequence identity to comprising a polypeptide from about amino acid 9 to about amino acid 76 or from about amino acid 95 to about amino acid 160 SEQ ID NO: 2;
(c) a polypeptide having at least 99% sequence identity to comprising a polypeptide from about amino acid 9 to about amino acid 75 or from about amino acid 98 to about amino acid 158 SEQ ID NO: 3; or
(d) a polypeptide having at least 99% sequence identity to comprising a polypeptide from about amino acid 9 to about amino acid 75 or from about amino acid 93 to about amino acid 158 of SEQ ID NO: 4.
4. The method of claim 2 , wherein the isolated or recombinant polypeptide is a mammalian polypeptide that is or is not post-translationally modified, a mammalian polypeptide that is or is not post-translationally alkylated, and a polypeptide expressed in a non-mammalian system.
5. The method of claim 4 , wherein the mammalian polypeptide is a human polypeptide.
6. The method of claim 1 , wherein the isolated or recombinant polypeptide comprising an HMG-box (high mobility group-box) domain comprises one or more of:
(a) a polypeptide comprising from about amino acid 6 to about amino acid 76 or from about amino acid 90 to about amino acid 138 of SEQ ID NO: 1;
(b) a polypeptide comprising from about amino acid 9 to about amino acid 76 or from about amino acid 95 to about amino acid 160 SEQ ID NO: 2;
(c) a polypeptide comprising nucleotides from about amino acid 9 to about amino acid 75 or from about amino acid 98 to about amino acid 158 SEQ ID NO: 3; or
(d) a polypeptide comprising nucleotides from about amino acid 9 to about amino acid 75 or from about amino acid 93 to about amino acid 158 of SEQ ID NO: 4.
7. The method of claim 1 , wherein the isolated or recombinant polypeptide comprising the HMG-box domain comprises one or more of:
(a) an isolated or recombinant polypeptide high mobility group box 1 (HMGB1) consisting of from about amino acid 6 to about amino acid 76 of SEQ ID NO: 1 or a polypeptide having at least 98% sequence identity thereto;
(b) an isolated or recombinant polypeptide high mobility group box 2 (HMGB2) consisting of from about amino acid 9 to about amino acid 76 of SEQ ID NO: 2 or a polypeptide having at least 98% sequence identity thereto;
(c) an isolated or recombinant polypeptide high mobility group box 3 (HMGB3) consisting of from about amino acid 9 to about amino acid 75 of SEQ ID NO: 3 or a polypeptide having at least 98% sequence identity thereto; or
(d) an isolated or recombinant polypeptide high mobility group box 4 (HMGB 4) consisting of from about amino acid 9 to about amino acid 75 of SEQ ID NO: 4 or a polypeptide having at least 98% sequence identity thereto.
8. The method of claim 7 , wherein the isolated or recombinant polypeptide is a mammalian polypeptide that is or is not post-translationally modified, a mammalian polypeptide that is or is not post-translationally alkylated, and a polypeptide expressed in a non-mammalian system.
9. The method of claim 8 , wherein the mammalian polypeptide is a human polypeptide.