Treatment of intracellular bacterial infection

Abstract

An intracellular bacterial infection in a plant or animal is treated by administration to a plant cell or animal cell of a particle to which an infectious bacteriophage is covalently attached, wherein the particle is internalised by the cell. Particles with phage attached and compositions comprising the particles are provided. A formulation, for treatment of a bacterial infection, comprises bacteriophage, liquid carrier and adhesive, which dries so that the adhesive adheres the bacteriophage to a surface, one such formulation comprising liquid carrier: 85%-99.98% by weight; bacteriophage: 0.01%-5% by weight; and adhesive: 0.01%-10% by weight.

1 . A method of treatment or prevention of an intracellular bacterial infection in a plant or animal, comprising administering to a plant cell or animal cell of a particle to which an infectious bacteriophage is covalently attached, wherein the particle is internalized by the cell. 
     
     
         2 . The method of  claim 1 , wherein the particle is 1 micron or less in a diameter. 
     
     
         3 . The method of  claim 2 , wherein the particle is 0.5 microns or less in diameter. 
     
     
         4 . The method of  claim 2 , wherein the particle is 10 nanometers or more in diameter. 
     
     
         5 . The method of  claim 1 , wherein the particle is administered by inhalation or injection. 
     
     
         6 . The method of  claim 2 , wherein the bacteriophage infects  Yersinia  spp.,  Neisseria gonorrhoeae, Shigella  spp.,  Listeria  spp.,  Salmonella enterica, Salmonella enterica  serovar  Typhimurium, Legionella pneumophila, Coxiella burnettii, Francisella tularensis, Mycobacteria  spp.,  Chlamydia  spp.,  Escherichia coli, Rickettsia  spp.,  Brucella  spp.,  Ehrlichia  spp. or  Burkholderia mallei.    
     
     
         7 . (canceled) 
     
     
         8 . A method of treatment of an intracellular bacterial infection in a human macrophage, comprising administering to the macrophage a particle of diameter 1 micron or less to which an infectious bacteriophage is covalently attached. 
     
     
         9 . The method of  claim 1 , comprising administering to the plant a particle of 5 microns or less in diameter to which an infectious bacteriophage is covalently attached. 
     
     
         10 . The method of  claim 9 , wherein the particle is 1 micron or less in diameter. 
     
     
         11 . The method of  claim 10 , wherein the particle is 0.5 microns or less in diameter. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 9 , wherein the particle is administered as an aerosol. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 9 , wherein the particle is administered to the roots. 
     
     
         16 . The method of  claim 9 , wherein the particle is administered through being introduced into the xylem or phloem. 
     
     
         17 . The method of  claim 9 , wherein the bacteriophage infects bacteria of the genera  Pseudomonas, Erwinia, Pectobacterium, Pantoea, Agrobacterium, Ralstonia, Burkholderia, Acidovorax, Xanthomonas, Clavibacter, Streptomyces, Xylella, Spiroplasma  or  Phytoplasma.    
     
     
         18 - 20 . (canceled) 
     
     
         21 . A composition comprising a plurality of particles of mean diameter 1 microns or less, wherein one or more infectious bacteriophages is covalently attached thereto. 
     
     
         22 - 23 . (canceled) 
     
     
         24 . The composition of  claim 21 , comprising multiple bacteriophages, wherein the bacteriophages are active against different strains of bacteria. 
     
     
         25 . The composition of  claim 21 , wherein the particle is made of a biodegradable material. 
     
     
         26 . The composition of  claim 21 , wherein the particles are modified to increase uptake and/or internalization of the particle by a plant or animal cell. 
     
     
         27 . The composition of  claim 21 , wherein the particle is functionalized by the addition of carboxyl groups. 
     
     
         28 - 43 . (canceled) 
     
     
         44 . The method of  claim 6 , wherein the bacteriophage infects  Shigella flexneri, Listeria monocytogenes , or  Mycobacterium tuberculosis.