Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios

Patent metadata

Field	Value
Publication number	US-9573908-B2
Application number	US-201314381432-A
Country	US
Kind code	B2
Filing date	Feb 20, 2013
Priority date	Feb 27, 2012
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

Using a whole-cell high-throughput screen, eleven molecules were identified that activate V. cholerae quorum sensing (QS). Eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. Pro-QS molecules are used for the development of novel anti-infectives.

First claim

The invention claimed is:

1. A compound from the group consisting of:

2. A method for inhibiting virulence of gram negative quorum sensing Vibrio bacteria that employ the quorum sensing response regulator LuxO, the method comprising contacting gram negative quorum sensing Vibrio bacteria that comprise the quorum sensing response regulator LuxO with a compound from a group consisting of

in an amount that inhibits the quorum sensing response regulator LuxO.

3. The method of claim 2 wherein the bacteria are Vibrio cholerae or Vibrio parahaemolyticus.

4. A method for prophylactic treatment of a host organism, including but not limited to humans, domesticated or wild mammals, domesticated or wild avian species, domesticated or wild fish, and domesticated or wild mollusks, at risk for an imminent and potentially deleterious infection with a member of the vibrio species of bacteria, to inhibit bacterial pathogenicity of Vibrio bacteria that employ the quorum sensing response regulator LuxO, the method comprising contacting gram negative quorum sensing Vibrio bacteria that comprise the quorum sensing response regulator LuxO with a compound from a group consisting of

in an amount that inhibits the quorum sensing response regulator LuxO.

5. A method for inhibiting biofilm formation by gram negative quorum sensing Vibrio bacteria that employ the quorum sensing response regulator LuxO, the method comprising contacting the Vibrio bacteria that comprise the quorum sensing response regulator LuxO with a compound from a group consisting of

in an amount that inhibits the quorum sensing response regulator LuxO.

Assignees

• Bassler Bonnie L
• Ng Wai-Leung
• Perez Lark J
• Cong Jianping
• Semmelhack Martin F
• Univ Princeton

Inventors

• Bassler Bonnie L
• Ng Wai-Leung
• Perez Lark J
• Cong Jianping
• Semmelhack Martin F

Classifications

• A01N43/707

  1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines · CPC title

• C07F7/10

  containing nitrogen {having a Si-N linkage} · CPC title

• A01N55/00

  Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur (containing organo-phosphorus compounds A01N57/00) · CPC title

• C07D253/075 Primary

  Two hetero atoms, in positions 3 and 5 · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title