Use of bile acids and bile salts as anti bacterial agents for inhibition of bacterial conjugation and horizontal gene transfer

11077,123

16/080672

February 28, 2017

Methods of inhibiting bacterial conjugation, bacterial horizontal gene transfer or bacterial growth are disclosed. The methods comprise contacting bacteria with an effective amount of a bile acid or a bile salt, wherein the effective amount does not affect viability of the bacteria. A method of increasing susceptibility of bacteria to antibiotic treatment is also disclosed as well as methods of decontaminating a farm animal housing or a medical surface and methods of treating water. Also disclosed are compositions effective in inhibiting bacterial conjugation, bacterial horizontal gene transfer and bacterial growth.

Tel HaShomer Medical Research Infrastructure and Services Ltd. (Ramat-Gan, IL)

Tel HaShomer Medical Research Infrastructure and Services Ltd. (Ramat-Gan, IL)

1. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, and wherein when said bile acid or bile salt is comprised in a composition comprising antibiotics, said antibiotics are selected from the group consisting of penicillin, clavulanate acid, trimethoprim-sulfamethoxazole, fluoroquinolone, cephalosporin, macrolide, azalide, sulfonamide, ampicillin, tetracycline, chloramphenicol, minocycline, doxycycline, vancomycin, bacitracin, kanamycin, neomycin, gentamycin, erythromycin, spectinomycin, zeomycin and streptomycin, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer.

2. The method of claim 1 , wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals.

3. The method of claim 1 , wherein said bile salt comprises an amino acid conjugated bile acid.

4. The method of claim 3 , comprising a taurine conjugated bile acid or a glycine conjugated bile acid.

5. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer of enteric bacteria, the method comprising contacting enteric bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said effective amount does not affect viability of said bacteria, and wherein when said bile acid or bile salt is comprised in a composition comprising antibiotics, said antibiotics are selected from the group consisting of penicillin, clavulanate acid, trimethoprim-sulfamethoxazole, fluoroquinolone, cephalosporin, macrolide, azalide, sulfonamide, ampicillin, tetracycline, chloramphenicol, minocycline, doxycycline, vancomycin, bacitracin, kanamycin, neomycin, gentamycin, erythromycin, spectinomycin, zeomycin and streptomycin, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer of said enteric bacteria.

6. The method of claim 5 , wherein said enteric bacteria are resistant to said bile acid or said bile salt.

7. The method of claim 5 , wherein said enteric bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals.

8. The method of claim 5 , wherein said bile salt comprises an amino acid conjugated bile acid.

9. The method of claim 8 , comprising a taurine conjugated bile acid or a glycine conjugated bile acid.

10. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, and wherein said bile acid or said bile salt is not co-formulated with an antibiotics.

11. The method of claim 10 , wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals.

12. The method of claim 10 , wherein said bile salt comprises an amino acid conjugated bile acid.

13. The method of claim 12 , comprising a taurine conjugated bile acid or a glycine conjugated bile acid.

14. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a composition consisting of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer.

15. The method of claim 14 , wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals.

16. The method of claim 14 , wherein said bile salt comprises an amino acid conjugated bile acid.

17. The method of claim 16 , comprising a taurine conjugated bile acid or a glycine conjugated bile acid.

18. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, and wherein said bile acid or bile salt is comprised in a composition comprising antibiotics, said antibiotics are selected from the group consisting of penicillin, clavulanate acid, trimethoprim-sulfamethoxazole, fluoroquinolone, cephalosporin, macrolide, azalide, sulfonamide, ampicillin, tetracycline, chloramphenicol, minocycline, doxycycline, vancomycin, bacitracin, kanamycin, neomycin, gentamycin, erythromycin, spectinomycin, zeomycin and streptomycin, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer.

19. The method of claim 18 , wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals.

20. The method of claim 18 , wherein said bile salt comprises an amino acid conjugated bile acid.

21. The method of claim 20 , comprising a taurine conjugated bile acid or a glycine conjugated bile acid.

22. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, and wherein the method further comprises contacting said bacteria with antibiotics, said bile salt or said bile acid and said antibiotics not being co-formulated, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer.

23. The method of claim 22 , wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals.

24. The method of claim 22 , wherein said bile salt comprises an amino acid conjugated bile acid.

25. The method of claim 24 , comprising a taurine conjugated bile acid or a glycine conjugated bile acid.

26. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, and wherein said contacting is by coating, spraying, misting, soaking, dispersing, powdering, flushing, wiping, dipping, rinsing, spreading, wetting, immersing, painting or adhering to a surface, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer.

27. The method of claim 26 , wherein said surface is selected from the group consisting of a fabric, a fiber, a foam, a film, a concrete, a masonry, a glass, a metal, a plastic, a rubber, a polymer, or combinations thereof.

28. A method of inhibiting bacterial conjugation or bacterial horizontal gene transfer, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt, wherein said bile acid comprises lithocholic acid or glycocholic acid or salt thereof at a concentration of 1-5% (w/v), wherein said bacteria are resistant to said bile acid or said bile salt, and wherein said effective amount does not affect viability of said bacteria, and wherein said bile acid or said bile salt is attached to a surface, thereby inhibiting the bacterial conjugation or bacterial horizontal gene transfer.

29. The method of claim 28 , wherein said bile acid or said bile salt coats said surface.

30. The method of claim 28 , wherein said surface is selected from the group consisting of a fabric, a fiber, a foam, a film, a concrete, a masonry, a glass, a metal, a plastic, a rubber, a polymer, or combinations thereof.

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