Compositions and methods for detoxifying bacterial endotoxins

Abstract

Compositions comprising a rhodanese with a phosphate-binding motif and methods of detoxifying bacterial endotoxins with such compositions.

What is claimed is: 
     
         1 . A composition comprising a population of microorganisms engineered to produce a composition comprising an engineered or non-naturally occurring rhodanese comprising a phosphate-binding motif, wherein the phosphate-binding motif comprises a sequence of CX 1 X 2 X 3 X 4 X 5 R, wherein each of X 1 -X 5  represents a single amino acid. 
     
     
         2 . The composition of  claim 1 , wherein the microorganisms are probiotic bacteria. 
     
     
         3 . The composition of  claim 1 , wherein the composition is a food product, a nutritional formulation, a dairy product, or a combination thereof. 
     
     
         4 . The composition of  claim 3 , wherein the food product comprises a plant or a part thereof. 
     
     
         5 . The composition of  claim 3 , wherein the dairy product is non-pasteurized diary, partially pasteurized milk, a milk component, or a milk fat globule membrane component. 
     
     
         6 . The composition of  claim 1 , wherein X 1  is E or R;
 X 2  is Y, F, E, T, K, or G;   X 3  is S or G;   X 4  is S or G; and   X 5  is V or E.   
     
     
         7 . The composition of claim  28 , wherein the phosphate-binding motif comprises a sequence of SEQ ID NOs. 3-15. 
     
     
         8 . The composition of claim  29 , wherein the phosphate-binding motif comprises a sequence of SEQ ID NO. 3. 
     
     
         9 . The composition of  claim 1 , wherein the rhodanese comprises a sequence of SEQ ID NO. 16. 
     
     
         10 . The composition of  claim 1 , wherein the rhodanese has a dephosphorylation activity. 
     
     
         11 . The composition of  claim 1 , wherein the rhodanese is capable of dephosphorylating a bacterial endotoxin. 
     
     
         12 . The composition of  claim 11 , wherein the bacterial endotoxin is lipopolysaccharide (LPS) or lipoteichoic acid (LTA). 
     
     
         13 . The composition of  claim 1 , wherein the rhodanese is or is derived from a mammalian intestine rhodanese, human rhodanese, or bovine liver rhodanese or synthetic polypeptides contain modified rhodanese domains. 
     
     
         14 . A pharmaceutical formulation comprising the composition of  claim 1 . 
     
     
         15 . The pharmaceutical formulation of  claim 14 , further comprising a stabilizer, activator, carrier, osmotic agent, propellant, disinfectant, protective agent, diluent, nutritional agent, excipient, or a combination thereof. 
     
     
         16 . A method for treating a health condition induced by a bacterial endotoxin, the method comprising administering a composition comprising an effective amount of the composition of  claim 1 . 
     
     
         17 . The method of  claim 16 , wherein the health condition is a LPS-mediated, LPS-induced, or LPS-exacerbated disease. 
     
     
         18 . The method of  claim 16 , wherein the health condition is bowel diseases,  Clostridium difficile  infection, modulation of gut microbiota, alternation of bacterial over growth, Small intestinal bacterial overgrowth, antibiotic-associated diarrhea (AAD), gastrointestinal tract infections, abdominal infections, sepsis, septic shock, systemic inflammatory response syndrome, meningococcemia, trauma, hemorrhagic shock, burns, surgery, organ transplantation, liver diseases, pancreatitis, enterocolitis, periodontal diseases, pneumonia, cystic fibrosis, asthma, coronary heart diseases, congestive heart failure, kidney diseases, hypophosphatasia, hemolytic uremic syndrome, renal dialysis, preserving renal function, autoimmune diseases, cancers, Alzheimer's disease, rheumatoid arthritis, lupus, systemic lupus erythematosus, metabolic disorders, obesity, diabetes, dyslipidemia, insulin resistant syndromes, metabolic syndrome, steatohepatitis, fatty liver, non-alcoholic fatty liver diseases, hyperglycemia, glucose intolerance, impaired glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL levels, high LDL levels, abdominal obesity, atherosclerosis, hypertension, and cardiovascular diseases, or a combination thereof. 
     
     
         19 . The method of  claim 16 , wherein the composition is effective to increase the number of commensal bacteria in the gastrointestinal tract, decrease the number of pathogenic bacteria in the gastrointestinal tract, or increase the number of commensal bacteria and decrease the number of pathogenic bacteria in the gastrointestinal tract, thereby modulating gastrointestinal tract flora levels in the subject.