IP Library Granted Patent US 8,609,110
Granted Patent B2
US 8,609,110 · App. 13/528,633 · Granted Dec 17, 2013

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Quick Facts
Patent No.
US 8,609,110
App. No.
13/528,633
Granted
Dec 17, 2013
Kind
B2
Abstract

Provided herein are methods for treating planktonic bacteria or a biofilm. The methods include contacting the planktonic bacteria or biofilm with an effective amount of an isolated Citrobacter freundii colicin A polypeptide, wherein the polypeptide has an antibacterial activity against the planktonic bacteria or the biofilm. Methods are also provided herein for treating a subject that has a bacterial infection, for example caused by a biofilm. The methods can be used to treat a biofilm on a living or non-living surface. Also provided herein are Citrobacter freundii colicin A polypeptides that have an antibacterial activity against planktonic bacteria or surface attached bacteria, and nucleic acid sequences encoding the polypeptides. Medical devices comprising a surface having an antimicrobial effective amount of a Citrobacter freundii colicin A polypeptide, or a nucleic acid molecule encoding the polypeptide, are also disclosed.

Claims (28)

1. An isolated polypeptide, comprising the amino acid sequence set forth as SEQ ID NO: 1, wherein the polypeptide has an antibacterial activity against a biofilm.

2. A composition comprising the polypeptide of claim 1 .

3. The composition of claim 2 , further comprising one or more compounds selected from the group consisting of a carrier, diluent, adjuvant, solubilizing agent, and suspending agent.

4. The composition of claim 2 , further comprising a second antibacterial agent, an antifungal agent, or an antiprotozoal agent.

5. A pharmaceutical composition, comprising the polypeptide of claim 1 and a pharmaceutical carrier.

6. A medical device comprising a surface, wherein the surface comprises an antimicrobial effective amount of the polypeptide of claim 1 .

7. The medical device of claim 6 , wherein the polypeptide is incorporated into a polymeric coating on the medical device surface.

8. A method for treating a biofilm, comprising contacting the biofilm with an effective amount of an antibacterial agent, wherein the agent comprises the isolated polypeptide of claim 1 and wherein the isolated polypeptide has an antibacterial activity against the biofilm, thereby treating the biofilm.

9. The method of claim 1 , further comprising selecting for treatment a surface infected with a biofilm.

10. The method of claim 1 , wherein the biofilm is on a medical device suitable for surgical implantation within the body.

11. The method of claim 10 , wherein the medical device is a catheter, a stent, a shunt, an endotracheal tube, a gastric feeding tube, a prosthetic joint, an intrauterine device, a voice prosthesis, a central venous catheter, a tympanostomy tube, a prosthetic heart valve, or a pacemaker.

12. The method of claim 1 , wherein treating the biofilm reduces biofilm cell viability by at least 2%, at least 5%, at least 10%, at least 20%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 99%, or 100%.

13. The method of claim 1 , wherein the biofilm comprises Gram-negative bacteria.

14. The method of claim 13 , wherein the Gram-negative bacteria comprise the family Enterobacteriacae.

15. The method of claim 14 , wherein the Enterobacteriacae bacteria comprise a genus selected from the group consisting of Citrobacter, Enterobacter, Escherichia, Klebsiella , and Yersinia.

16. The method of claim 12 , further comprising one or more additional administrations of the isolated polypeptide to inhibit growth of the biofilm.

17. The method of claim 1 , further comprising contacting the biofilm with an effective amount of a second antibacterial agent.

18. The method of claim 1 , further comprising contacting the biofilm with an effective amount of an antifungal agent or an antiprotozoal agent.

19. A method for treating a subject infected with a biofilm, comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an antibacterial agent, wherein the antibacterial agent comprises the isolated polypeptide of claim 1 and wherein the isolated polypeptide has an antibacterial activity against the biofilm, thereby treating the subject.

20. The method of claim 19 , wherein the biofilm is on a medical device implanted in the subject.

21. The method of claim 20 , wherein the medical device is a catheter, a stent, a shunt, an endotracheal tube, a gastric feeding tube, a prosthetic joint, an intrauterine device, a voice prosthesis, a central venous catheter, a tympanostomy tube, a prosthetic heart valve, or a pacemaker.

22. The method of claim 19 , wherein treating the subject reduces biofilm cell viability by at least 2%, at least 5%, at least 10%, at least 20%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 99%, or 100%.

23. The method of claim 22 , further comprising one or more additional administrations of the pharmaceutical composition to the subject to inhibit further growth of the bacterial biofilm.

24. The method of claim 19 , wherein the biofilm comprises Gram-negative bacteria.

25. The method of claim 24 , wherein the Gram-negative bacteria comprise the family Enterobacteriacae.

26. The method of claim 25 , wherein the bacteria comprises a genus selected from the group consisting of Citrobacter, Enterobacter, Escherichia, Klebsiella , and Yersinia.

27. The method of claim 19 , further comprising administering to the subject a therapeutically effective amount of a second antibacterial agent.

28. The method of claim 19 , further comprising administering to the subject a therapeutically effective amount of an antifungal agent or an antiprotozoal agent.

Assignments (4)
NUNC PRO TUNC ASSIGNMENT Recorded Sep 5, 2013
From: THE UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY
To: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Reel/Frame 031170/0331 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 21, 2012
From: SHANKS, ROBERT M.Q.
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 029002/0668 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 21, 2012
From: KADOURI, DANIEL E.
To: UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY
Reel/Frame 029002/0701 →
CONFIRMATORY LICENSE Recorded Sep 18, 2012
From: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 029003/0260 →