Multiple host range bacteriophage with hybrid tail fibres
AssigneePhico Therapeutics Ltd.
InventorsHeather Fairhead, Adam Wilkinson, Katy Pitts, Anne Barnard, Emmanuele Severi, Neil Anderson
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Abstract
Modified bacteriophage, uses thereof, and compositions containing the modified bacteriophage are described. The compositions are useful for human treatment and may treat various conditions, including bacterial infections.
Claims19
A modified bacteriophage, capable of infecting a plurality of different target bacteria, which bacteriophage includes an α/β small acid-soluble spore protein (SASP) gene encoding a SASP which is toxic to the target bacteria;
- wherein the bacteriophage is non-lytic;
- and wherein the bacteriophage expresses a hybrid host range determinant protein which comprises an amino acid sequence from a plurality of different bacteriophages;
- wherein said bacteriophage comprises an inactivated lysis gene, and wherein the hybrid host range determinant protein comprises a tail fibre protein comprising a receptor binding region for binding to the target bacteria and a region linking the receptor binding region to the body of the bacteriophage, wherein the receptor binding region is a C-terminal receptor binding region and the region linking the C-terminal receptor binding region to the body of the bacteriophage is an N-terminal region, and wherein each of the C-terminal and N-terminal regions are from a different bacteriophage than each other;
- and further wherein the N-terminal region comprises amino acids 1 to 628 of the tail fibre protein and the C-terminal region comprises amino acids 629 to 964 of the tail fibre protein, based on the amino acid sequence of bacteriophage Phi33, and/or wherein the C-terminal region has no more than 96% amino acid sequence identity with the C-terminal region of bacteriophage Phi33.
A modified bacteriophage capable of infecting a plurality of different Pseudomonas target bacteria, which bacteriophage includes an α/β small acid-soluble spore protein (SASP) gene encoding a SASP which is toxic to the target bacteria;
- wherein the bacteriophage is non-lytic;
- and wherein the bacteriophage expresses a hybrid host range determinant protein which comprises an amino acid sequence from a plurality of different bacteriophages, wherein the hybrid host range determinant comprises a hybrid tail fibre protein, or a tail fibre protein which comprises a receptor binding region for binding to the target bacteria and a region linking the receptor binding region to the body of the bacteriophage, wherein the receptor binding region is a C-terminal receptor binding region and the region linking the C-terminal receptor binding region to the body of the bacteriophage is an N-terminal region, wherein each of the C-terminal and N-terminal regions are from a different bacteriophage, wherein the N-terminal region comprises amino acids 1 to 628 of the tail fibre protein and the C-terminal region comprises amino acids 629 to 964 of the tail fibre protein, based on the amino acid sequence of bacteriophage Phi33, and wherein the C-terminal region has no more than 96% amino acid sequence identity with the C-terminal region of bacteriophage Phi33, and wherein the N-terminal region has at least 95% amino acid sequence identity with the N-terminal region of bacteriophage Phi33.
A modified bacteriophage capable of infecting a plurality of different target bacteria, which bacteriophage includes an α/β small acid-soluble spore protein (SASP) gene encoding a SASP which is toxic to the target bacteria;
- wherein the bacteriophage expresses a hybrid host range determinant protein which comprises an N-terminal region and a C-terminal region from different bacteriophages,
- wherein the N-terminal region comprises amino acids of a first bacteriophage having at least 95% identity to amino acids 1 to 628 of the tail fibre protein of bacteriophage Phi33 and the C-terminal region comprises amino acids of a second bacteriophage corresponding to amino acids 629 to 964 of the tail fibre protein of bacteriophage Phi33, and wherein the C-terminal region has no more than 96% amino acid sequence identity with the C-terminal region of amino acids 629 to 964 of bacteriophage Phi33.
Dependencies are inferred from the claim text.