Lactobacillus acidophilus surface layer protein a (SlpA) as a therapeutic agent for the treatment of inflammatory diseases

Patent metadata

Field	Value
Publication number	US-11028135-B2
Application number	US-202016804020-A
Country	US
Kind code	B2
Filing date	Feb 28, 2020
Priority date	Oct 24, 2014
Publication date	Jun 8, 2021
Grant date	Jun 8, 2021

Abstract

The current invention provides a recombinant bacterium, the recombinant bacterium being genetically modified to decrease or eliminate the display of lipoteichoic acid (LTA), surface layer protein B (SlpB) and surface layer protein X (SlpX) on the surface of said bacterium. Efficacious therapies for a subject suffering from an inflammation mediated disease are also provided. The methods of the current invention comprise administering to a subject in need thereof a therapeutically effective amount of the recombinant L. acidophilus cells or a therapeutically effective amount of the isolated surface layer protein A (SlpA) or a non-naturally occurring derivative thereof. The recombinant L. acidophilus cells or SlpA isolated from L. acidophilus can be in a pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or excipient. In an embodiment of the invention, the pharmaceutical composition is administered orally.

First claim

We claim:

1. A recombinant lactic acid bacterium that is genetically modified to express a polypeptide comprising SEQ ID NO: 4 or a polypeptide that is at least 95% identical to SEQ ID NO: 4 and does not express (i) a polypeptide comprising SEQ ID NO: 1 or orthologs thereof or a polypeptide having at least 95% sequence identity to SEQ ID NO: 1; (ii) a polypeptide comprising SEQ ID NO: 2 or orthologs thereof or a polypeptide having at least 95% sequence identity to SEQ ID NO: 2; and (iii) a polypeptide comprising SEQ ID NO: 3 or orthologs thereof or a polypeptide having at least 95% sequence identity to SEQ ID NO: 3.

2. The recombinant lactic acid bacterium according to claim 1 , wherein said recombinant bacterium is a Lactobacillus strain.

3. The recombinant lactic acid bacterium according to claim 2 , wherein the Lactobacillus strain is L. lactis.

4. The recombinant lactic acid bacterium according to claim 1 , wherein said bacterium lacks genes encoding SEQ ID NO: 1 or orthologues thereof, SEQ ID NO: 2 or orthologues thereof, and SEQ ID NO: 3 or orthologues thereof.

5. The recombinant lactic acid bacterium according to claim 1 , wherein said bacterium does not express (i) a polypeptide having at least 95% sequence identity to SEQ ID NO: 1; (ii) a polypeptide having at least 95% sequence identity to SEQ ID NO: 2; and (iii) a polypeptide having at least 95% sequence identity to SEQ ID NO: 3.

6. A probiotic food comprising the recombinant lactic acid bacterium of claim 1 .

Assignees

• Univ Florida

Inventors

• Lightfoot Yaima L
• Sahay Bikash
• Mohamadzadeh Mansour

Classifications

• A61K38/164

  from bacteria · CPC title

• A61K35/747

  Lactobacilli, e.g. L. acidophilus or L. brevis · CPC title

• A61K38/13

  Cyclosporins · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• C12N15/746

  for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus) · CPC title