Clostridioides difficile
AssigneeImperial College of Science, Technology and Medicine
InventorsJulian Marchesi, Julie Mcdonald, Benjamin Mullish
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Abstract
The invention relates to Clostridioides difficile, and in particular to compounds, polypeptides and mixtures for the treatment of C. difficile infections. The invention also relates to nucleic acids, vectors comprising these nucleic acids and microorganisms for the treatment of C. difficile infections, and to methods of identifying and matching faecal microbiota transplant (FMT) donors to FMT recipients.
Claims25
A method of treating, preventing or ameliorating a Clostridioides difficile infection, the method comprising administering, to a subject in need thereof, a therapeutically effective amount of a compound of Formula (I):
- wherein R1 is a C2 to C10 alkyl or halogenated alkyl;
- and
- R2 is hydrogen or a C1 to C4 alkyl or halogenated alkyl, and the C1 to C4 alkyl or halogenated alkyl is optionally substituted with between 1 and 5 substituents, wherein each substituent has the formula:
- wherein each R3 is independently a C2 to C10 alkyl or halogenated alkyl;
- or a pharmaceutically acceptable salt solvate, tautomeric form or polymorphic form thereof.
A method of treating, preventing or ameliorating a Clostridioides difficile infection, the method comprising administering, to a subject in need thereof, a therapeutically effective amount of a bile salt hydrolase (BSH) or an active variant thereof, or a succinate-metabolising enzyme or active variant thereof.
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A method of treating, preventing or ameliorating a Clostridioides difficile infection, the method comprising administering, to a subject in need thereof, a therapeutically effective amount of:
- (i) a vector comprising a nucleic acid sequence encoding a bile salt hydrolase (BSH) or an active variant thereof;
- (ii) a microorganism expressing a bile salt hydrolase (BSH) or an active variant thereof;
- or (iii) a microorganism capable of converting short or medium chain fatty acid precursors present in the gut, to short or medium chain fatty acids.
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A method of selecting a faecal microbiota transplant (FMT) donor, for FMT in a subject suffering from a Clostridioides difficile infection, the method comprising:
- (i) analysing, in a sample obtained from a potential FMT donor, the concentration of a short or medium chain fatty acid, bile acids, enzymes associated with the production of a short or medium chain fatty acid, and/or bile salt hydrolase (BSH), or the enzymatic activity thereof, or an expression product thereof;
- and
- (ii) comparing this concentration, or enzymatic activity thereof, or expression product thereof, with a reference value from a control population for the concentration of the short or medium chain fatty acid, bile acid, enzymes associated with the production of a short or medium chain fatty acid, and/or bile salt hydrolase (BSH), or the enzymatic activity thereof, or the expression product thereof, wherein an FMT donor is selected as having;
- (a) a higher concentration of short or medium chain fatty acid, enzymes associated with the production of a short or medium chain fatty acid and/or BSH, or the enzymatic activity thereof, or the expression product thereof, relative to the respective reference value;
- and/or
- (b) a lower concentration of bile acids that stimulate Clostridioides difficile germination, relative to the respective reference value;
- and/or
- (c) a higher concentration of bile acids that inhibit Clostridioides difficile vegetative growth, relative to the respective reference value.
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Dependencies are inferred from the claim text.