Claims
- 1. A synthetic oligonucleotide complementary to a transcript of the marORAB operon which inhibits expression of the operon.
- 2. The oligonucleotide of claim 1 wherein the gene whose expression is inhibited is selected from the group consisting of marO, marO/R, marR, marR/A, and marA.
- 3. The oligonucleotide of claim 1 wherein the oligonucleotide contains at least one internucleotide linkage selected from the group consisting of alkylphosphonates, phosphorothioates, phosphorodithioates, alkylphosphonothioates, phosphoramidates, phosphate esters, carbamates, acetamidate, carboxymethyl esters, carbonates, and phosphate triesters.
- 4. The oligonucleotide of claim 3 wherein the synthetic oligonucleotide contains at least one phosphorothioate internucleotide linkage.
- 5. The oligonucleotide of claim 1 comprising at least one deoxyribonucleotide.
- 6. The oligonucleotide of claim 1 comprising at least one ribonucleotide.
- 7. The oligonucleotide of claim 5 comprising at least one ribonucleotide.
- 8. The oligonucleotide of claim 1 wherein the oligonucleotide is from about 15 to 21 nucleotides in length.
- 9. The oligonucleotide of claim 1 having a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, NO:2, NO: 3, NO:4, NO: 5, and NO: 6.
- 10. A method of inhibiting expression of the marORAB operon comprising the step of contacting a transcript of the marORAB operon nucleic acid with a synthetic oligonucleotide complementary to the transcript.
- 11. The method of claim 10 wherein the oligonucleotide is complementary to a transcript of a gene selected from the group consisting of marO, marO/R, marR, marR/A, and marA.
- 12. The method of claim 11 wherein the oligonucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, NO: 2, NO: 3, NO: 4, NO: 5, and NO: 6.
- 13. A method of reducing bacterial resistance to an antibiotic comprising exposing a bacteria in a subject with an infection to a synthetic oligonucleotide complementary to a transcript of the marORAB operon such that bacterial resistance to an antibiotic is reduced.
- 14. The method of claim 13 wherein said oligonucleotide is administered to the subject in a pharmaceutical carrier.
- 15. The method of claim 14, comprising administering in addition at least one antibiotic to the subject.
- 16. The method of claim 15, wherein the antibiotic is selected from the group consisting of a penicillin, a cephalosporin, an aminoglycoside, a sulfonamide, a macrolide, a tetracycline, a lincoside, a quinolone, a chloramphenicol, a vancomycin, a rifampin, an isoniazid, or a trimethoprim.
- 17. The method of claim 13, wherein the oligonucleotide is complementary to a transcript of a locus selected from the group consisting of marO, marO/R, marR, marR/A, and marA.
- 18. The method of claim 13, wherein the oligonucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, NO: 2, NO: 3, NO: 4, NO: 5, and NO: 6.
- 19. The method of claim 18, wherein the bacteria are exposed to at least two synthetic oligonucleotides having a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, NO: 2, NO: 3, NO: 4, NO: 5, and NO: 6.
- 20. The method of claim 13, wherein the infection in the subject is a species of Escherichia, Salmonella, Shigella, Klebsiella, Citrobacter, Hafnia, or Enterobacter.
- 21. A method of treatment for a bacterial infection in a subject by administering to the subject a therapeutic amount of a synthetic oligonucleotide complementary to a transcript of the marORAB operon.
- 22. The method of claim 21, wherein the bacterial infection comprises infection with at least one bacterium having multiple drug resistance.
- 23. The method of claim 21 wherein the subject is additionally administered an antibiotic.
- 24. The method of claim 23, wherein the antibiotic is selected from the group consisting of a penicillin, a cephalosporin, an aminoglycoside, a sulfonamide, a macrolide, a tetracycline, a lincoside, a quinolone, a chloramphenicol, a vancomycin, a rifampin, an isoniazid, or a trimethoprim.
- 25. The method of claim 21, wherein the infection comprises an Escherichia, a Salmonella, a Shigella, a Klebsiella, a Citrobacter, a Hafnia, or an Enterobacter.
- 26. The method of claim 21 wherein the oligonucleotide is complementary to a transcript of a gene selected from the group consisting of marO, marO/R, marR, marR/A, and marA.
- 27. The method of claim 26 wherein the oligonucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, NO: 2, NO: 3, NO: 4, NO: 5, and NO: 6.
- 28. A pharmaceutically acceptable composition comprising a synthetic oligonucleotide complementary to a transcript of marORAB operon which inhibits the expression of a locus in the operon; and a physiologically acceptable carrier.
- 29. The pharmaceutically acceptable composition of claim 28 wherein the oligonucleotide is complementary to a transcript of a gene selected from the group consisting of marO, marO/R, marR, marR/A, and marA.
- 30. The pharmaceutically acceptable composition of claim 28 wherein the oligonucleotide has a nucleotide sequence consisting essentially of SEQ ID NO: 1, NO: 2, NO: 3, NO: 4, NO: 5, and NO: 6.
RELATED APPLICATION
[0001] This application claims priority to the U.S. Provisional Application Serial No. 60/038,663, entitled “OLIGONUCLEOTIDES SPECIFC FOR THE marORAB OPERON AND METHODS OF THEIR USE”, filed Feb. 21, 1997, the contents of which are expressly incorporated by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60038663 |
Feb 1997 |
US |
Continuations (2)
|
Number |
Date |
Country |
Parent |
09596390 |
Jun 2000 |
US |
Child |
10153275 |
May 2002 |
US |
Parent |
09027130 |
Feb 1998 |
US |
Child |
09596390 |
Jun 2000 |
US |