Methods for identifying candidate compounds for treating, reducing, or preventing pathogenic infections
Disclosed are methods for identifying candidate compounds for treating, reducing, or preventing a pathogenic infection, the methods including: (a) contacting a pathogenic cell with a candidate compound; and (b) measuring the production of a molecule selected from the group consisting of an 4-hydroxy-2-alkylquinoline (HAQ) molecule, 4-hydroxy-2-heptylquinoline (HHQ) molecule, or a derivative or precursor thereof in the cell, a candidate compound that reduces the production relative to production of the molecule by a cell not contacted with the candidate compound, identifying a candidate compound useful for treating, reducing, or preventing a pathogenic infection.
1. A method for identifying a compound that reduces production of a 4-hydroxy-2-alkylquinoline (HAQ) molecule, 4-hydroxy-2-heptylquinoline (HHQ) molecule, or a derivative or precursor thereof, said method comprising:
(a) contacting a Pseudomonas cell with a compound;
(b) measuring the production of a molecule selected from the group consisting of a HAQ molecule, HHQ molecule, or a derivative or precursor thereof in said Pseudomonas cell; and
(c) comparing the production of said molecule in step (b) relative to production of said molecule by said Pseudomonas cell when not contacted with said compound, thereby identifying said compound tha reduces production of said HAQ molecule, HHQ molecule, or a derivative or precursor thereof,
wherein said HAQ molecule, said HHQ molecule, or said derivative or precursor thereof is selected from any one of the following:
wherein R 1 , R 2 , and R 4 are independently —C 5 H 11 , —C 6 H 13 , —C 7 H 15 , —C 8 H 17 , —C 9 H 19 , —C 11 H 23 , —C 7 H 13 , —C 8 H 15 , —C 9 H 17 , or —C 11 H 21 ;
R 3 is —C 5 H 11 , —C 6 H 13 , —C 7 H 15 , —C 8 H 17 , —C 9 H 19 , —C 11 H 23 , —C 9 H 17 , or —C 11 H 21 ;
R 5 is —C 5 H 11 , —C 6 H 13 , —C 7 H 15 , —C 8 17 , —C 9 H 19 , or —C 11 H 23 .
2. The method of claim 1 , wherein step (b) comprises measuring the HAQ molecule.
3. The method of claim 1 , wherein said Pseudomonas cell infects a mammal.
4. The method of claim 3 , wherein said mammal is a human.
5. The method of claim 1 , wherein said Pseudomonas cell infects a plant.
6. The method of claim 1 , wherein said Pseudomonas cell is Pseudomonas aeruginosa.
7. The method of claim 6 , wherein said Pseudomonas aeruginosa is Pseudomonas aeruginosa PA14 or Pseudomonas aeruginosa PA01.
8. The method of claim 1 , wherein said molecule is selected from the group consisting of
wherein R 1 and R 2 are independently —C 5 H 11 , —C 6 H 13 , —C 7 H 15 , —C 8 H 17 , —C 9 H 19 , —C 11 H 23 , —C 7 H 13 , —C 8 H 15 , —C 9 H 17 , or —C 11 H 21 .
9. The method of claim 1 , wherein said HHQ is
wherein R 3 is —C 5 H 11 , —C 6 H 13 , —C 7 H 15 , —C 8 H 17 , —C 9 H 19 , —C 11 H 23 , —C 9 H 17 , or —C 11 H 21 .