Small molecule antagonists of bacterial quorum-sensing receptors
A novel small molecule antagonizes two types of acyl homoserine lactone receptors: membrane-bound and cytoplasmic. A focused library of analogs and derivatives of the original antagonist was synthesized. Analog and derivative molecules harbor a range of activities. The novel small molecule and most potent antagonist protects the eukaryote Caenorhabditis elegans from quorum-sensing-mediated killing by the bacterial pathogen Chromobacterium violaceum . The saving of C. elegans demonstrates the use of these molecules as small molecule antimicrobials.
1. A method of disrupting detection of acyl-homoserine lactone-type autoinducer in Gram-negative bacteria comprising contacting the bacteria with a small molecule represented by the formula:
2. A method of inhibiting infection of a host by quorum sensing bacteria comprising contacting the bacteria with a small molecule represented by the formula:
3. The method of claim 2 wherein a therapeutically effective amount of the small molecule is administered to the host.
4. A method of controlling growth of quorum sensing Gram-negative bacteria that attach to a solid surface, comprising exposing the bacteria to a composition comprising one or more of the small molecules represented by the formula:
in an amount that affects biofilm formation.
5. The method of claim 4 wherein the composition is applied to the surface.
6. The method of claim 4 wherein the composition is administered to a host infected with the bacteria.
7. A method of inhibiting quorum sensing-mediated activity in Gram-negative bacteria comprising contacting the bacteria with a small molecule represented by the formula:
8. The method of claim 7 wherein the activity is bioluminescence, siderophore production, type III secretion, or metalloprotease production.
9. The method of claim 7 wherein the activity is production of virulence factors.
10. The method of claim 9 wherein the bacterial species is selected from the group consisting of V. harveyi, C. violaceum and P. aeroginosa.
11. The method of claim 9 wherein the bacterial species is C. violaceum.
12. The method of claim 9 wherein the bacteria are pathogenic to humans or animals.
13. The method of claim 9 wherein the bacteria are pathogenic to plants.
14. The method of claim 9 wherein the bacteria are pathogenic to marine life.
15. The method of claim 7 wherein the small molecule is the chlorolactone.