Identification of bacterial autoinducer and use in treating bacterial pathogenicity
A bacterial autoinducer, CAI-1, was purified and its structure identified. Methods for synthesis of the autoinducer and its analogues were elucidated. Methods of using the autoinducer or its analogues for treating bacterial pathogenicity and bio film formation are described. Methods for prevention and treatment of cholera are described. Synthetic (S)-3-hydroxytridecan-4-one functions as well as natural CAI-1 in repressing production of the virulence factor toxin co-regulated pilus (TCP). Strategies are described to manipulate bacterial quorum sensing in the clinical arena.
1. A purified compound that is (S)-3-hydroxytridecan-4-one, (R)-3-hydroxytridecan-4-one, (S)-3-hydroxydodecan-4-one, (R)-3-hydroxydodecan-4-one, (S)-3-hydroxyundecan-4-one, or (R)-3-hydroxyundecan-4-one.
2. A composition comprising the compound of claim 1 wherein the composition inhibits biofilm formation.
3. A composition comprising at least one compound recited in claim 1 wherein the composition inhibits virulence in V. cholerae.
4. A method of inhibiting quorum-sensing-dependent activity in Vibrio spp. comprising contacting the Vibrio bacteria with an effective amount of the compound of claim 1 .
5. The method of claim 4 wherein the quorum-sensing-dependent activity is bio film formation.
6. The method of claim 4 wherein the quorum-sensing-dependent activity is pathogenicity.
7. The method of claim 6 wherein the pathogenicity is caused by production of a virulence factor that comprises TCP.
8. The method of claim 4 wherein the bacteria are V. cholerae, V. harveyi, V. anguillarum, V. alginolyticus, V. parahaemolyticus, V. furnissi, V. angustum, V. proteolyticus or V. vulnificus.
9. The method of claim 4 wherein the bacteria are V. campbelli, V. spledidus , or V. shilonii.
10. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.
11. A method for repressing V. cholerae pathogenicity comprising contacting V. cholerae bacteria with the compound of claims 1 and (S)-4,5-dihydroxypentane-2,3-dione (DPD).
12. A method for repressing V. cholerae pathogenicity comprising contacting V. cholerae bacteria with (S)-3-hydroxytridecan-4-one (CAI-1) and (S)-4,5-dihydroxypentane-2,3-dione (DPD).
13. A composition for use in the treatment of cholera in a subject wherein said composition comprises the compound of claim 1 with a diluent or carrier.
14. A purified compound that is (S)-3-hydroxydodecan-4-one, (R)-3-hydroxydodecan-4-one, (S)-3-hydroxyundecan-4-one, or (R)-3-hydroxyundecan-4-one.