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

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.

1 . (canceled) 
     
     
         2 . A recombinant bacterium that is genetically modified to express a polypeptide comprising SEQ ID NO: 4 or a polypeptide that is at least 90% 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 90% sequence identity to SEQ ID NO: 1; (ii) a polypeptide comprising SEQ ID NO: 2 or orthologs thereof or a polypeptide having at least 90% 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 90% sequence identity to SEQ ID NO: 3. 
     
     
         3 . The recombinant bacterium according to  claim 2 , wherein said recombinant bacterium is a  Lactobacillus  strain. 
     
     
         4 . The recombinant bacterium according to  claim 3 , wherein the  Lactobacillus  strain is selected from the group consisting of  L. acidophilus, L. amylolyticus, L. amylovorus, L. brevis, L. brevis  ssp  gravesensis, L. buchneri, L. crispatus, L. gallinarum, L. gigeriorum, L. helveticus/suntoryeus, L. hilgardii, L. kefiranofaciens, L. pasteurii, L. lactis  and  L. ultunensis.    
     
     
         5 . The recombinant bacterium according to  claim 2 , 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. 
     
     
         6 . The recombinant bacterium according to  claim 2 , wherein said bacterium does not express (i) a polypeptide having at least 90% sequence identity to SEQ ID NO: 1; (ii) a polypeptide having at least 90% sequence identity to SEQ ID NO: 2; and (iii) a polypeptide having at least 90% sequence identity to SEQ ID NO: 3. 
     
     
         7 . A probiotic food comprising the recombinant bacterium of  claim 2 . 
     
     
         8 . A method of treating an inflammatory disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the recombinant bacterium of  claim 2  or a composition comprising said recombinant bacterium. 
     
     
         9 . The method according to  claim 8 , wherein the recombinant bacterium is orally administered to the subject. 
     
     
         10 . The method according to  claim 8 , wherein the inflammatory disease is selected from the group consisting of allergies, ankylosing spondylitis, Crohn's disease, diabetes, Type I diabetes, gastroesophageal reflux disease, Hashimoto's thyroiditis, hyperthyroidism, hypothyroidism, Irritable Bowel Syndrome (IBS), interstitial cystitis (IC), Lofgren's syndrome, lupus erythematosis, myasthenia gravis, multiple sclerosis, osteoarthritis, polymyalgia rheumatica, prostatitis, psoriasis, psoriatic arthritis, Raynaud's syndrome/phenomenon, reactive arthritis (Reiter syndrome), restless leg syndrome, reflex sympathetic dystrophy (RSD), rheumatoid arthritis, scleroderma, Sjögren's syndrome, ulcerative colitis and uveitis.