Modified bacteriophage

Abstract

A modified bacteriophage capable of infecting a plurality of different target bacteria, which bacteriophage includes a toxin gene encoding a toxin protein which is toxic to the target bacteria; wherein the bacteriophage is lytic; and wherein the bacteriophage expresses host range determinant proteins which have a plurality of bacterial host specificities.

1 . A modified bacteriophage capable of infecting a plurality of different target bacteria, which bacteriophage includes a toxin gene encoding a toxin protein which is toxic to the target bacteria; wherein the bacteriophage is lytic; and wherein the bacteriophage expresses host range determinant proteins which have a plurality of bacterial host specificities. 
     
     
         2 - 45 . (canceled) 
     
     
         46 . A modified bacteriophage capable of infecting a plurality of different target bacteria, which bacteriophage comprises a variant of bacteriophage Phi33 which has been modified to comprise an α/β small acid-soluble spore protein (SASP) gene encoding a SASP gene which is expressed under the control of a constitutive promoter, and further wherein the bacteriophage is lytic. 
     
     
         47 . A modified bacteriophage according to  claim 46 , wherein the tail fiber protein comprises a receptor binding region that binds to the target bacterium and a region linking the receptor binding region to the body of the bacteriophage. 
     
     
         48 . A modified bacteriophage according to  claim 46 , wherein the constitutive promoter is selected from pdhA, rspB, pgi, fda, and lasB. 
     
     
         49 . A modified bacteriophage according to  claim 46 , wherein the constitutive promoter is fda. 
     
     
         50 . A modified bacteriophage according to  claim 46 , wherein the SASP is SASP-C. 
     
     
         51 . A modified bacteriophage according to  claim 50 , wherein the SASP-C is from  Bacillus megaterium.    
     
     
         52 . A modified bacteriophage according to  claim 46 , wherein the target bacteria includes  Pseudomonas.    
     
     
         53 . A modified bacteriophage according to  claim 46 , wherein the target bacteria includes  Pseudomonas aeruginosa.    
     
     
         54 . A composition comprising a modified bacteriophage according to  claim 46 , and a pharmaceutically acceptable carrier. 
     
     
         55 . A composition comprising a modified lytic bacteriophage according to  claim 46  in admixture with at least one other modified lytic bacteriophage which is capable of infecting target bacteria, which also includes a SASP gene encoding a SASP which is toxic to a target bacteria. 
     
     
         56 . A composition according to  claim 55 , which comprises at least two of said modified lytic bacteriophages, wherein at least two of which have different host specificities. 
     
     
         57 . A modified bacteriophage according to  claim 46 , which comprises a SASP-C gene comprised of  P. aeruginosa  optimized codons, which gene is operably linked to the fda promoter. 
     
     
         58 . A modified bacteriophage according to  claim 46 , which consists of a variant of bacteriophage Phi33 wherein the modifications consist of the incorporation of a SASP-C gene which is comprised of  P. aeruginosa  optimized codons, and which gene is operably linked to the fda promoter, and further wherein the bacteriophage is lytic. 
     
     
         59 . A composition according to  claim 54  which is formulated for pharmaceutical use, for topical use, or for delivery to the respiratory tract. 
     
     
         60 . A composition according to  claim 58  which is formulated for pharmaceutical use, for topical use, or for delivery to the respiratory tract. 
     
     
         61 . A method of killing target bacteria comprising contacting said target bacteria with a bactericidally effective amount of at least one modified bacteriophage according to  claim 46 , which is toxic to the target bacteria. 
     
     
         62 . A method of killing target bacteria comprising contacting said target bacteria with a bactericidally effective amount of at least one modified bacteriophage according to  claim 58 , which is toxic to the target bacteria. 
     
     
         63 . The method of  claim 61 , which is effected in vitro. or in vivo, by administering a bactericidally effective amount of said modified bacteriophage to a subject infected by said target bacterium. 
     
     
         64 . The method of  claim 62 , which is effected in vitro. or in vivo, by administering a bactericidally effective amount of said modified bacteriophage to a subject infected by said target bacterium.