Anti-bacterial compositions comparing lytic modified bacteriophage engineered to infect and kill different target bacteria
Inventors
Fairhead, Heather • Wilkinson, Adam
Assignees
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Publication Number
US-11732243-B2
Publication Date
2023-08-22
Expiration Date
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.
Core Innovation
The invention provides an antibacterial platform comprising an isolated modified lytic bacteriophage engineered to infect multiple different target bacteria. The modified lytic bacteriophage comprises a toxin gene encoding a toxin protein toxic to the target bacteria, wherein the toxin gene comprises an α/β small acid-soluble spore protein (SASP) gene, and the toxin function is incorporated into a lytic bacteriophage composition.
The platform expresses one or more host range determinant proteins not naturally present in the bacteriophage to broaden bacterial host specificity. The host range determinant proteins comprise tail fibre proteins that include a receptor binding region for binding to the target bacteria and a region linking the receptor binding region to the body of the bacteriophage, including tail fibre variants with hybrid N-/C-terminal regions.
The described support includes comparison against phage cocktails and against non-lytic SASPjects, including manufacturing viability and increased in vivo potency. The documented examples include construction of a three-phage mixture and evaluation using in vitro time-kill and in vivo murine efficacy studies, together with propagation and lysate titre data demonstrating production despite the presence of the toxic SASP gene.
Claims Coverage
The document recites one independent claim directed to a bacteriophage-based antibacterial composition, with multiple dependent claims refining the toxin/SASP elements, expression control, tail fibre structure, target bacteria scope, and multi-phage mixture composition. The independent claim establishes two inventive features: an α/β SASP-containing toxin gene in a modified lytic bacteriophage and engineered tail fibre host range determinants for multiple bacterial host specificities.
Modified lytic bacteriophage with toxin gene comprising α/β SASP
The composition includes at least one isolated modified lytic bacteriophage modified to comprise a toxin gene encoding a toxin protein toxic to the target bacteria, wherein the toxin gene comprises an α/β small acid-soluble spore protein (SASP) gene.
Engineered tail fibre host range determinants for multiple host specificities
The composition includes a modified lytic bacteriophage that expresses one or more host range determinant proteins not naturally present in the bacteriophage, wherein the host range determinant proteins comprise tail fibre proteins with a receptor binding region for binding to the target bacteria and a region linking the receptor binding region to the body of the bacteriophage.
The inventive focus is on combining a lytic bacteriophage carrying an α/β SASP-containing toxin gene with engineered tail fibre proteins that provide host-range determinant functions, formulated with a pharmaceutically acceptable carrier and intended to inhibit target bacterial growth in vivo and/or in target environments.
Stated Advantages
Increased in vivo potency.
Manufacturing viability.
More effective approach than phage cocktails.
More effective approach than non-lytic SASPjects.
Documented Applications
Inhibiting the growth of target bacteria when administered to a subject infected with the target bacteria and/or when applied to an environment comprising the target bacteria.
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