A live genetically engineered gram-negative bacterium, comprising:
- a first heterologous gene which encodes at least a first subunit of a functional multimeric cytolethal distending toxin or a fusion of a first subunit of the functional multimeric cytolethal distending toxin, the first heterologous gene being inducible or repressible via a first promoter or operator;
- repressor,
- a second heterologous gene which encodes at least a second subunit of the functional multimeric cytolethal distending toxin or a fusion of the second subunit of the functional multimeric cytolethal distending toxin, the second heterologous gene being inducible or repressible via a second promoter or operator repressor;
- the first promoter or operator repressor being independent and different from the second promoter or operator repressor;
- the first heterologous gene being responsive via the first promoter or operator and the second heterologous gene being responsive via the second promoter or operator, to together implement a Boolean logic function selected from the group consisting of NOT, NOR, NAND, OR, AND, XOR, and Not XOR, with respect to formation by the live genetically engineered gram-negative bacterium of the functional multimeric cytolethal distending toxin;
- being configured to functionally implement a Boolean logic function based on inputs represented by presence or absence of a first inducer or repressor for the respective first promoter or operator repressor and by presence or absence of a second inducer or repressor for the second promoter or operator repressor, the first promoter or operator repressor and the second promoter or operator repressor being adapted to selectively interact to provide a different functional outcome than independent promotion or repression of the first heterologous gene or promotion or repression of the second heterologous gene;
- and
- an output representing a gene product selectively transcribed in dependence on the presence or absence induction or repression of the first promoter or operator repressor and the second promoter or operator repressor and the Boolean logic function, wherein the output provides feedback to the Boolean logic function,
- the live genetically engineered gram-negative bacterium being adapted for administration to a human or animal and colonization of at least one tissue under non-lethal conditions;
- and the functional multimeric cytolethal distending toxin gene product has a tissue-specific therapeutic effect on the human or animal.