Sublancin lantibiotic produced by Bacillus subtilis 168

• US 6,541,607 B1
• Filed: 04/17/2000
• Issued: 04/01/2003
• Est. Priority Date: 07/18/1997
• Status: Expired due to Fees

• Current Assignee: University of Maryland
• Original Assignee: University of Maryland
• Inventors: Hansen, J. Norman
• Primary Examiner(s): Carlson, Karen Cochrane
• Assistant Examiner(s): Robinson, Hope A.
• Application Number:
  US09/462,478
• Time in Patent Office: 1,079 Days
• Field of Search: 530/350, 530/300, 424/93.1, 514/2, 514/21
• US Class Current: 530/350
• CPC Class Codes: A23L 3/34635 Antibiotics
• CPC Class Codes: A23L 3/3526 Organic compounds containing nitrogen
• CPC Class Codes: A23L 3/3571 Microorganisms; Enzymes
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/32 from Bacillus (G)

Abstract

An antimicrobial peptide produced by Bacillus subtilis 168 was isolated and characterized and named sublancin 168. The invention includes DNA encoding for the sublancin 168 peptides and peptides which are at least 80% identical to the sublancin 168 peptide. The peptides may be administered as anti-bacterials, or may be used in food preservation. The peptides may also be co-administered with other lantibiotics (such as nisin and subtilin), or with known antibiotics.

Claims

1. An isolated peptide having an amino acid sequence which is at least 80% identical with SEQ ID NO:

7 prior to dehydration of serines and threonines and formation of thioether cross-linkages, wherein the peptide is a lantibiotic.

4. The peptide of claim 1, wherein the amino acid sequence is at least 90% identical with SEQ ID NO:

7.

5. The peptide of claim 1, wherein the amino acid sequence is 100% identical with SEQ ID NO:

7.

2. An isolated peptide having an amino acid sequence which is at least 80% identical with SEQ ID NO:

5 prior to dehydration of serines and threonines and formation of thioether cross-linkages, wherein the peptide is a lantibiotic.

3. The peptide of claim 2, wherein a thioether cross-linkage is formed between the amino acids of positions 19 and 22 and disulfide cross-linkages are formed between the amino acids of positions 7 and 36 and positions 14 and 29.

6. A peptide having an amino acid sequence which is at least 80% identical with SEQ ID NO:

5 prior to dehydration of serines and threonines and formation of thioether cross-linkages.

7. The peptide of claim 6, wherein the amino acid sequence is at least 90% identical with SEQ ID NO:

5.

8. The peptide of claim 6, wherein the amino acid sequence is 100% identical with SEQ ID NO:

5.

9. An isolated peptide having an amino acid sequence which is at least 80% identical with SEQ ID NO:

18, wherein the peptide is a lantibiotic.

10. The peptide of claim 9, wherein a thioether cross-linkage is formed between the amino acids of positions 19 and 22 and disulfide cross-linkages are formed between the amino acids of positions 7 and 36 and positions 14 and 29.

11. The peptide of claim 9, wherein the amino acid sequence is at least 90% identical with SEQ ID NO:

18.

12. The peptide of claim 9, wherein the amino acid sequence is 100% identical with SEQ ID NO:

18.

13. A pharmaceutical preparation suitable for treating a bacterial infection, comprising the peptide of claim 9 in combination with a pharmaceutically acceptable carrier.

14. A method of treating a bacterial infection in a patient in need thereof, comprising administering to the patient an effective amount of the peptide of claim 9.

15. The method of claim 14, wherein the bacteria is a gram-positive bacteria.

16. A method of inhibiting bacterial growth in a food, comprising adding to the food an effective amount of an isolated peptide having an amino acid sequence which is at least 80% identical with SEQ ID NO:

18, wherein the peptide is a lantibiotic.

17. The method of claim 16, wherein the bacteria is a gram-positive bacteria.

18. A method for inhibiting the spore outgrowth of gram positive bacteria comprising contacting said bacteria with a composition comprising an isolated peptide having an amino acid sequence which is at least 80% identical with SEQ ID NO:

18, wherein the peptide is a lantibiotic.