Control of spore germination
AssigneeThe Trustees of Columbia University in the City of New York
InventorJonathan Dworkin
Life of this patent
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Abstract
Provided are compositions and methods for treating bacterial infections. It is demonstrated herein that bacteria cell wall materials stimulate germination of spores of Gram-positive bacteria, and that such activity requires Ser/Thr kinase PrkC. By modulating one or both, spores (which can be antibiotic resistant) can be stimulated or inhibited from germination, which can be exploited in various methods of therapeutic treatment. Also provided is a method of modulating germination of a spore of a Gram-positive bacterium. Also provided is a method of decontaminating an environment.
Claims23
A method of treating an infection of a first spore-forming Gram-positive bacterium comprising:
- administering to a subject in need thereof an effective amount of
- (A) a first composition comprising at least one of
- (i) a peptidoglycan fragment or muropeptide of a second bacterium or a preparation comprising cell walls from the second bacterium;
- (ii) a compound that stimulates activity of a bacterial serine/threonine protein kinase;
- or
- (iii) a compound that inhibits activity of a bacterial PPM-like phosphatase;
- wherein said first composition stimulates germination of the spore;
- or
- (B) a second composition comprising at least one of
- (iv) a compound that inhibits activity of a bacterial serine/threonine protein kinase;
- or
- (v) a compound that stimulates activity of a PPM-like phosphatase of a first Gram-positive bacterium;
- wherein said second composition inhibits germination of the spore.
A pharmaceutical composition comprising:
- an antibiotic effective against a Gram-positive bacterium;
- and
- at least one of
- (A) a first composition comprising at least one of
- (i) a peptidoglycan fragment or muropeptide of a second bacterium or a preparation comprising cell walls from the second bacterium;
- (ii) a compound that stimulates activity of a serine/threonine protein kinase of a Gram-positive bacterium;
- or
- (iii) a compound that inhibits activity of a PPM-like phosphatase of a Gram-positive bacterium;
- wherein said first composition stimulates germination of a Gram-positive bacterium spore;
- or
- (B) a second composition comprising at least one
- (iv) a compound that inhibits activity of a bacterial serine/threonine protein kinase;
- or
- (v) a compound that stimulates activity of a PPM-like phosphatase of a first Gram-positive bacterium;
- wherein said second composition inhibits germination of a Gram-positive bacterium spore;
- and
- a pharmaceutically acceptable carrier or excipient.
A method of decontaminating an environment containing spores of a first Gram-positive bacterium comprising:
- treating the environment with a composition comprising at least one of
- (i) a peptidoglycan fragment or muropeptide of a second bacterium or a preparation comprising cell walls from the second bacterium;
- (ii) a compound that stimulates activity of a serine/threonine protein kinase of a Gram-positive bacterium;
- or
- (iii) a compound that inhibits activity of a PPM-like phosphatase of a Gram-positive bacterium.
A method of modulating germination of a spore of a first Gram-positive bacterium comprising:
- contacting the spore of the first Gram-positive bacterium with
- (A) a first composition comprising at least one of
- (i) a peptidoglycan fragment or muropeptide of a second bacterium or a preparation comprising cell walls from the second bacterium;
- (ii) a compound that stimulates activity of a serine/threonine protein kinase of a Gram-positive bacterium;
- or
- (iii) a compound that inhibits activity of a PPM-like phosphatase of a Gram-positive bacterium;
- wherein said first composition stimulates germination of the spore;
- or
- (B) a second composition comprising at least one
- (iv) a compound that inhibits activity of a bacterial serine/threonine protein kinase;
- or
- (v) a compound that stimulates activity of a PPM-like phosphatase of a first Gram-positive bacterium;
- wherein said second composition inhibits germination of the spore.
Dependencies are inferred from the claim text.