Attenuated live bacteria with increased acid resistance and methods of use thereof
AssigneeArizona Board of Regents on behalf of Arizona State University
InventorsRoy Curtiss, III, Karen Brenneman, Kenneth Roland
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Abstract
The present invention relates to inducing acid resistance in a bacterium and methods of increasing the acid resistance of an acid sensitive bacterium.
Claims20
A recombinant attenuated derivative of a pathogenic enteric bacterium comprising at least one of the following:
- a) a regulatable promoter operably linked to a nucleic acid encoding an arginine decarboxylase and a nucleic acid encoding an arginine agmatine antiporter;
- b) a regulatable promoter operably linked to a nucleic acid encoding a glutamate decarboxylase and a nucleic acid encoding a glutamate/γ-aminobutyric acid antiporter;
- or
- c) a regulatable promoter operably linked to a nucleic acid encoding a lysine decarboxylase and a nucleic acid encoding a lysine/cadaverine antiporter.
A method for increasing the acid resistance of an acid sensitive bacterium, the method comprising introducing into the acid sensitive bacterium a cassette comprising at least one of the following:
- a) a regulatable promoter operably linked to a nucleic acid encoding an arginine decarboxylase and a nucleic acid encoding an arginine agmatine antiporter;
- b) a regulatable promoter operably linked to a nucleic acid encoding a glutamate decarboxylase and a nucleic acid encoding a glutamate/γ-aminobutyric acid antiporter;
- or
- c) a regulatable promoter operably linked to a nucleic acid encoding a lysine decarboxylase and a nucleic acid encoding a lysine/cadaverine antiporter,
- such that in the absence of induction of the regulatable promoter, the recombinant bacterium is acid sensitive, but upon induction of the regulatable promoter, the recombinant bacterium displays an increase in acid resistance.
A recombinant Salmonella bacterium, the bacterium comprising a regulatable promoter operably linked to at least one nucleic acid selected from the group consisting of:
- a) adiA and adiC;
- b) gadB and gadC;
- and
- c) cadB and cadA.
Dependencies are inferred from the claim text.