Inhibition of quorum sensing-mediated processes in bacteria
Methods are provided for identifying molecules that can be used to positively and negatively manipulate quorum-sensing-mediated communication to control bacterial behavior. Small-molecule antagonists that disrupt quorum-sensing-mediated activities are identified. Methods are provided for disrupting detection of acyl-homoserine lactone autoinducer in Gram-negative bacteria by contacting the bacteria with the antagonists. Methods of inhibiting quorum sensing-mediated activity in Gram-negative bacteria are provided wherein the activity is pathogenicity, bioluminescence, siderophore production, type III secretion, or metalloprotease production.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, adjuvant or vehicle and a pharmaceutically-acceptable salt of a small molecule compound whose structure is selected from the group consisting of:
2. The pharmaceutical composition of claim 1 that is a solid dosage form.
3. The pharmaceutical composition of claim 2 that is in the form of capsules, tablets, pills, powders, tinctures or granules.
4. The pharmaceutical composition of claim 2 wherein the salt of the small molecule compound is admixed with at least one inert pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4 wherein the carrier is sucrose, lactose, or starch.
6. The pharmaceutical composition of claim 2 that comprises one or more lubricating agents.
7. The pharmaceutical composition of claim 3 that comprises a buffering agent.
8. The pharmaceutical composition of claim 3 that comprises an enteric coating.
9. A method of treatment for infection of a host by gram-negative quorum-sensing bacteria, which comprises administering to the host a therapeutically effective amount of the pharmaceutical composition of claim 1 .
10. The method of claim 9 that is administered orally, nasally, topically or parenterally.
11. The method of claim 9 for treatment for Vibrio bacteria infection.
12. A method of inhibiting infection of Vibrio bacteria in shellfish comprising contacting the bacteria with a small molecule a small molecule compound whose structure is selected from the group consisting of:
in a concentration sufficient to disrupt detection of autoinducer-1.