Bacterial DNA gyrase inhibitors and methods of use thereof
The subject invention provides fluorophore-quencher nucleic acid molecules comprising relaxed or supercoiled DNA molecules, and their use in rapid and efficient high-throughput screening (HTS) assays to screen and identify compounds that inhibit DNA gyrases. These compounds can be used as antibiotics for treating bacterial infections, especially, multidrug resistant bacterial infections.
1. A method for inhibiting a DNA gyrase, comprising contacting the DNA gyrase with compound 154; and measuring the DNA gyrase activity.
2. A method for treating a bacterial infection in a subject via the inhibition of DNA gyrase of the bacterium, the method comprising administering, to the subject in need of such treatment, a pharmaceutical composition comprising compound 154; and measuring bacterial growth, the bacterial infection being caused by E. coli, S. aureus , MRSA, or B. subtilis.
3. The method of claim 2 , said pharmaceutical composition being administered through oral, rectal, bronchial, nasal, topical, buccal, sub-lingual, transdermal, vaginal, intramuscular, intraperitoneal, intravenous, intra-arterial, intracerebral, or intraocular administration.
4. The method of claim 2 , the bacterial infection being caused by MRSA.
5. A method for inhibiting the growth of a bacterium, the method comprising contacting the bacterium with compound 154, measuring DNA gyrase activity in the bacterium and measuring the bacterial growth.
6. The method of claim 2 , the bacterial infection being caused by E. coli.
7. The method of claim 2 , the bacterial infection being caused by S. aureus.
8. The method of claim 2 , the bacterial infection being caused by B. subtilis.
9. The method of claim 5 , the bacterium being MRSA.
10. The method of claim 5 , the bacterium being M. tuberculosis.
11. The method of claim 5 , the bacterium being E. coli.
12. The method of claim 5 , the bacterium being S. aureus.
13. The method of claim 5 , the bacterium being B. subtilis.