Phage derived antimicrobial activities

Abstract

The present invention provides methods and compositions to reduce growth of microbial colonies, including infections, and includes therapeutic compositions, methods for treatment of infections, and methods for identifying additional such compositions.

1 . A chimeric Tail Associated Muralytic Enzyme (TAME) polypeptide, wherein the chimeric TAME polypeptide comprises a muralytic domain (MD) and a heterologous cell binding domain (CBD) that binds to a target bacterium, wherein the target bacterium exhibits reduced or no growth after being contacted with the chimeric TAME polypeptide. 
     
     
         2 . The chimeric TAME polypeptide of  claim 1 , wherein the MD has an activity selected from the group consisting of murein glycosidase, glucosaminidase, muraminidase, transglycosylase, lysozyme, amidase and endopeptidase activity. 
     
     
         3 . The chimeric TAME polypeptide of  claim 1 , wherein the MD is a catalytic domain from an ORF56 protein. 
     
     
         4 . The chimeric TAME polypeptide of  claim 1 , wherein the MD is selected from a catalytic domain from a lysostaphin protein, a catalytic domain from an ORF56 protein, and a catalytic domain from a LytM peptidase. 
     
     
         5 . The chimeric TAME polypeptide of  claim 1 , wherein the target bacterium is a  Staphylococcus  species. 
     
     
         6 . The chimeric TAME polypeptide of  claim 5 , wherein the target bacterium is a methicillin-resistant  Staphylococcus  species. 
     
     
         7 . The chimeric TAME polypeptide of  claim 1 , wherein the target bacterium is a slowly replicating bacterial species. 
     
     
         8 . A method of enzymatically degrading a cell wall of a bacterium, the method comprising contacting the cell wall with the chimeric TAME polypeptide of  claim 1 . 
     
     
         9 . A method of treating a bacterial infection in a subject in need of such treatment, the method comprising administering a pharmaceutical composition comprising the chimeric TAME polypeptide of  claim 1  to the subject. 
     
     
         10 . The method of  claim 9 , wherein the subject is a mammal. 
     
     
         11 . The method of  claim 10 , wherein the subject is selected from a human, a primate, a cow, a horse, a goat, a cat, a sheep, a rodent, a dog, and a pig. 
     
     
         12 . The method of  claim 11 , wherein the subject is a cow and the bacterial infection is bovine mastitis. 
     
     
         13 . The method of  claim 9 , wherein the subject is a bird. 
     
     
         14 . The method of  claim 13 , wherein the bird is a poultry species. 
     
     
         15 . The chimeric TAME polypeptide of  claim 1 , wherein the CBD is from a protein that is a member selected from the group consisting of an ORF56 protein and a lysostaphin protein. 
     
     
         16 . The chimeric TAME polypeptide of  claim 1 , wherein the MD is a catalytic domain from an ORF56 protein and the CBD is from a lysostaphin protein. 
     
     
         17 . A method of disinfecting a surface, the method comprising the step of contacting the surface with the chimeric TAME polypeptide of  claim 1 . 
     
     
         18 - 43 . (canceled)