REDUCTION OF GASTROINTESTINAL TRACT COLONISATION BY CAMPYLOBACTER

• US 20150025026A1
• Filed: 02/15/2013
• Published: 01/22/2015
• Est. Priority Date: 02/16/2012
• Status: Active Grant

• Current Assignee: Akeso Biomedical, Inc.
• Original Assignee: Akeso Biomedical, Inc.
• Inventors: Ala'Aldeen, Dlawer, Mahdavi, Jafar
• Granted Patent: US 9,655,912 B2
• Time in Patent Office: Days
• US Class Current: 514/25
• CPC Class Codes: A23K 20/111 Aromatic compounds
• CPC Class Codes: A23K 20/142 Amino acids; Derivatives thereof
• CPC Class Codes: A23K 50/75 for poultry
• CPC Class Codes: A61K 31/132 having two or more amino groups, e.g. spermidine, putrescine
• CPC Class Codes: A61K 31/136 having the amino group directly attached to the aromatic ring, e.g. benzeneamine
• CPC Class Codes: A61K 31/164 of a carboxylic acid with an aminoalcohol, e.g. ceramides
• CPC Class Codes: A61K 31/191 having two or more hydroxy groups, e.g. gluconic acid
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 31/7008 Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C12Q 1/18 Testing for antimicrobial activity of a material
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Campylobacter are the commonest reported bacterial causes of gastroenteritis in the UK and industrialized worlds. This invention relates to a method of preventing or reducing the colonisation of the gastrointestinal tract of an animal with Campylobacter. Accordingly, the present invention provides a method for disinfection of an animal comprising administering to said animal at least one compound that binds to MOMP or FlaA of Campylobacter in an effective amount to reduce the number of Campylobacter present in the gastrointestinal tract of said animal. The present invention also provides a method of preventing or reducing transmission of Campylobacter from one animal to another.

Claims

1. A method for treating or preventing Campylobacter colonization in an animal or meat product comprising administering at least one compound that binds to Major Outer Membrane Protein (MOMP) or the flagella (FlaA) of Campylobacter in an effective amount to reduce the number of Campylobacter present in the gastrointestinal tract of the animal or meat product.

2. The method of claim 1, wherein the Campylobacter is Campylobacter jejuni or Campylobacter Coli.

3. The method of claim 1, wherein the at least one compound is a compound that blocks the interaction of MOMP or FlaA with the cells of gastrointestinal tract.

4. The method of claim 1, wherein the compound specifically binds to at least one of amino acid residues Arg^3S2, Thr²⁶⁸, Lys²⁷⁸, Lys³⁸⁵, Asn²⁵⁸, Leu²⁹⁰, Tyr²⁹⁴, Phe³⁹⁵, Ile³³⁷, Arg³⁸¹, Asp²⁶¹, and Ser³⁹⁷ of MOMP (SEQ ID No. 1).

5. The method of claim 1, wherein the compound specifically binds to at least amino acid residue Thr²⁶⁸ of MOMP (SEQ ID NO. 1)

6. The method of claim 1, wherein the compound is a human histo blood group antigen or a synthetic human histo blood group antigen.

7. The method of claim 1, wherein the compound has a structure selected from the group consisting of:

8. The method of claim 1, wherein the compound is administered orally.

9. The method of claim 1, wherein the compound is administered in the animal'"'"'s feed or drinking water.

10. The method of claim 1, wherein the compound is administered daily between 3 and 5 days before slaughter of the animal.

11. The method of claim 1, wherein the compound is administered in an amount of 0.3-32 mg/day/kilo body weight of the animal.

12. The method of claim of claim 1 comprising the steps of:

providing an animal with a compound that binds to MOMP or FlaA of Campylobacter in an effective amount to reduce the number of Campylobacter present in the gastrointestinal tract of the animal; and

preparing a meat product from the animal.

13. The method of claim 12, wherein the animal is a poultry bird.

21. The method of claim 1 comprising administering the compound to a human.

22. The method of claim 1, wherein the compound prevents or reduces colonisation of the gastrointestinal tract of the animal with Campylobacter.

23. The method of claim 22, wherein the animal is poultry.

14. A method of identifying a compound for use in disinfection of animals, preventing or reducing adhesion of Campylobacter to the intestinal wall or treatment of Campylobacter infection in humans or animals, said method comprising the steps of:

a) providing a simulation of MOMP or glycosylated MOMP;

b) selecting a candidate molecule that fits within the cavity between loops 4 and 7 of MOMP or selecting a candidate molecule which interacts with at least one of amino acid residues Arg^3S2, Thr²⁶⁸, Lys²⁷⁸, Lys³⁸⁵, Asn²⁵⁸, Leu²⁹⁰, Tyr²⁹⁴, Phe³⁹⁵, Ile³³⁷, Arg³⁸¹, Asp²⁶¹, and Ser³⁹⁷ of MOMP (SEQ ID No.

     1).

15. The method of claim 14 further comprising the step of preparing a quantity of the selected compound.

16. An animal feed, feed ingredient or food supplement comprising a compound that binds to MOMP or FlaA of Campylobacter in an effective amount to reduce the number of Campylobacter present in the gastrointestinal tract of an animal.

17. The animal feed, feed ingredient or food supplement of claim 16 wherein the animal feed, feed ingredient or feed supplement is a feed, feed ingredient or feed supplement for poultry, preferably chickens.

18-20. -20. (canceled)

24. A kit comprising:

at least one compound that binds to MOMP or FlaA of Campylobacter and optionally instructions for using the kit.

25-29. -29. (canceled)