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US 12,735,714 B2Granted
Engineered dysbiosis-sensing probiotic for clostridium difficile infections and recurring infections management
AssigneeNational University of Singapore
InventorsElvin Koh, In Young Hwang, Matthew Wook Chang
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Abstract
The present invention relates to methods of metabolic engineering bacteria cells to produce bile salt hydrolase to inhibit the germination of C. difficile endospores and colonisation within the human gastrointestinal tract. The bile salt hydrolase is operably linked to a sialic acid-inducible promoter, pNanA, of which pNanA is in turn controlled by the repressor nanR. The recombinant bacteria expressing the bile salt hydrolase can be a probiotic strain to be used for prophylaxis or treatment of C. difficile infection.
Claims25
An expression cassette comprising;
- i. a bile salt hydrolase gene,
- ii. a sialic acid-responsive promoter for N-acetylneuraminate lyase (pNanA), operably linked to the bile salt hydrolase gene,
- iii. a pNanA repressor consisting of a N-acetylneuraminate repressor (NanR) protein-encoding polynucleotide operably linked to a constitutive promoter, and
- iv. an activator and promoter to increase the expression of the bile salt hydrolase gene, wherein the activator is a CadC protein (Cadmium resistance transcriptional regulatory protein)-encoding polynucleotide positioned downstream and under the control of pNanA, and the promoter is pCadBA (a promoter of lysine:
- cadaverine antiporter & lysine decarboxylase 1 genes) positioned downstream of the CadC protein-encoding polynucleotide and operably linked to the bile salt hydrolase gene.
2 more elements
Dependencies are inferred from the claim text.