# US 11,077,123 B2 · Use of bile acids and bile salts as anti bacterial agents for inhibition of bacterial conjugation and horizontal gene transfer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,123 B2 - Document ID: US11077123B2 - Status: Granted - Kind: B2 - Application number: 16/080,672 - Filed: 2017-02-28 - Published: 2019-03-07 - Granted: 2021-08-03 - Earliest claimed: 2016-02-29 - Assignees: Tel HaShomer Medical Research Infrastructure and Services Ltd. - Applicants: Tel HaShomer Medical Research Infrastructure and Services Ltd. - Inventors: Ohad Gal-Mor; Galia Rahav - Web page: https://patentgrep.com/patent/US11077123B2 ## CPC - A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol - A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61L 2/00: Disinfection or sterilisation of materials or objects, in general; Accessories therefor - A61P 31/04: Antibacterial agents - C02F 1/50: by addition or application of a germicide or by oligodynamic treatment {(C02F1/4606, C02F1/467, C02F1/76 take precedence)} - C02F 1/76: with halogens or compounds of halogens {(C02F1/4674 takes precedence)} - C02F 1/78: with ozone {(C02F1/4672 takes precedence)} - C02F 2303/04: Disinfection - C02F 2303/20: Prevention of biofouling - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C02F: TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE (separation in general B01D; special arrangements on waterborne vessels of installations for treating water, waste water or sewage, e.g. for producing fresh water, B63J; adding materials to water to prevent corrosion C23F; treating radioactively-contaminated liquids G21F9/04; regeneration of reactants for recirculation into processes, see the relevant places for the processes) ## Abstract 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. ## Claims ### Claim 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. ### Claim 2 (depends on 1) The method of claim 1, wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals. ### Claim 3 (depends on 1) The method of claim 1, wherein said bile salt comprises an amino acid conjugated bile acid. ### Claim 4 (depends on 3) The method of claim 3, comprising a taurine conjugated bile acid or a glycine conjugated bile acid. ### Claim 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. ### Claim 6 (depends on 5) The method of claim 5, wherein said enteric bacteria are resistant to said bile acid or said bile salt. ### Claim 7 (depends on 5) The method of claim 5, wherein said enteric bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals. ### Claim 8 (depends on 5) The method of claim 5, wherein said bile salt comprises an amino acid conjugated bile acid. ### Claim 9 (depends on 8) The method of claim 8, comprising a taurine conjugated bile acid or a glycine conjugated bile acid. ### Claim 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. ### Claim 11 (depends on 10) The method of claim 10, wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals. ### Claim 12 (depends on 10) The method of claim 10, wherein said bile salt comprises an amino acid conjugated bile acid. ### Claim 13 (depends on 12) The method of claim 12, comprising a taurine conjugated bile acid or a glycine conjugated bile acid. ### Claim 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. ### Claim 15 (depends on 14) The method of claim 14, wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals. ### Claim 16 (depends on 14) The method of claim 14, wherein said bile salt comprises an amino acid conjugated bile acid. ### Claim 17 (depends on 16) The method of claim 16, comprising a taurine conjugated bile acid or a glycine conjugated bile acid. ### Claim 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. ### Claim 19 (depends on 18) The method of claim 18, wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals. ### Claim 20 (depends on 18) The method of claim 18, wherein said bile salt comprises an amino acid conjugated bile acid. ### Claim 21 (depends on 20) The method of claim 20, comprising a taurine conjugated bile acid or a glycine conjugated bile acid. ### Claim 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. ### Claim 23 (depends on 22) The method of claim 22, wherein said bacteria are: enteropathogenic bacteria; and/or commensal or pathogenic bacteria to humans or animals. ### Claim 24 (depends on 22) The method of claim 22, wherein said bile salt comprises an amino acid conjugated bile acid. ### Claim 25 (depends on 24) The method of claim 24, comprising a taurine conjugated bile acid or a glycine conjugated bile acid. ### Claim 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. ### Claim 27 (depends on 26) 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. ### Claim 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. ### Claim 29 (depends on 28) The method of claim 28, wherein said bile acid or said bile salt coats said surface. ### Claim 30 (depends on 28) 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.