Compositions and methods for inhibiting the proliferation of enterotoxigenic bacteroides fragilis

Abstract

A composition for preventing or treating an infection or disease caused by enterotoxigenic Bacteroides fragilis includes a Siphoviridae bacteriophage (Bac-FRP-4) having an ability to lyse the enterotoxigenic Bacteroides fragilis cells and a pharmaceutically acceptable carrier. A method for preventing or treating an infection or disease caused by enterotoxigenic Bacteroides fragilis includes administering to a subject a Siphoviridae bacteriophage and lysing the enterotoxigenic Bacteroides fragilis cells by the Siphoviridae bacteriophage.

What is claimed is: 
     
         1 . A composition for preventing or treating an infection or disease caused by enterotoxigenic  Bacteroides fragilis  comprising:
 a Siphoviridae bacteriophage having an ability to lyse the enterotoxigenic  Bacteroides fragilis  cells, and   a pharmaceutically acceptable carrier.   
     
     
         2 . The composition of  claim 1 , wherein the Siphoviridae bacteriophage has a genome including a sequence as set forth in SEQ ID NO: 1; or a genome that has (1) a sequence having at least 90% query cover with at least 96% identity to SEQ ID NO: 1, (2) a circular genome topology, and (3) 67 open reading frames. 
     
     
         3 . The composition of  claim 1 , wherein the Siphoviridae bacteriophage has a concentration of 1×10 1  pfu/ml to 1×10 30  pfu/ml or 1×10 1  pfu/g to 1×10 30  pfu/g. 
     
     
         4 . The composition of  claim 3 , wherein the Siphoviridae bacteriophage has a concentration of 1×10 4  pfu/ml to 1×10 15  pfu/ml or 1×10 4  pfu/g to 1×10 15  pfu/g. 
     
     
         5 . The composition of  claim 1 , wherein the pharmaceutically acceptable carrier is lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil. 
     
     
         6 . The composition of  claim 1  further comprising:
 one or more selected from the group consisting of a lubricant, a wetting agent, a sweetener, a flavor, an emulsifier, a suspending agent, and a preservative. 
 
     
     
         7 . The composition of  claim 1 , wherein the infection or disease is acute and chronic intestinal disease, bacteremia, diarrhea, colitis, colonic neoplasia, or cancer. 
     
     
         8 . The composition of  claim 1 , wherein the composition is a solution, suspension, emulsion in oil, water-soluble medium, extract, powder, granule, tablet, or capsule. 
     
     
         9 . The composition of  claim 1 , wherein the Siphoviridae bacteriophage has major structural proteins in the sizes of approximately 25 kDa, 42 kDa, 48 kDa, and 65 kDa. 
     
     
         10 . The composition of  claim 1 , wherein the Siphoviridae bacteriophage has a latent period of 10-100 minutes and a burst size of 580-800 PFU/infected cell. 
     
     
         11 . The composition of  claim 10 , wherein the latent period is 40-80 minutes and the burst size of 240-330 PFU/infected cell. 
     
     
         12 . The composition of  claim 1  further comprising:
 a second bacteriophage having an ability to lyse enterotoxigenic  Bacteroides fragilis  bacterial species, 
 wherein the second bacteriophage has a genome that has a sequence having less than 90% query cover with at least 96% identity to SEQ ID NO: 1. 
 
     
     
         13 . A method for preventing or treating an infection or disease caused by enterotoxigenic  Bacteroides fragilis  (ETBF), comprising:
 administering to a subject a Siphoviridae bacteriophage; and   lysing ETBF cells by the Siphoviridae bacteriophage.   
     
     
         14 . The method of  claim 13 , wherein the Siphoviridae bacteriophage has a genome including a sequence as set forth in SEQ ID NO: 1. 
     
     
         15 . The method of  claim 13 , wherein the Siphoviridae bacteriophage has a concentration of 1×10 1  pfu/ml to 1×10 30  pfu/ml or 1×10 1  pfu/g to 1×10 30  pfu/g. 
     
     
         16 . The method of  claim 15 , wherein the Siphoviridae bacteriophage has a concentration of 1×10 4  pfu/ml to 1×10 15  pfu/ml or 1×10 4  pfu/g to 1×10 15  pfu/g.