WARF: P180110US02

  • Patent applied for.

Novel Inhibitors of Pseudomonas aeruginosa Quorum Sensing


Helen Blackwell, Daniel Manson

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing the most potent and efficacious compounds found to date that inhibit the P. aeruginosa quorum sensing receptor, LasR.
OVERVIEWThe Gram-negative pathogen Pseudomonas aeruginosa has a high rate of resistance to traditional antibiotics, posing a special risk to cystic fibrosis patients and others with compromised immune systems such as patients undergoing chemotherapy, burn survivors and people with AIDS.

Like other pathogens relevant to human health, P. aeruginosa regulates virulence and biofilm formation via quorum sensing. The quorum sensing receptor LasR is a leading target for antibacterial development, and synthetic molecules capable of modulating receptor-molecule binding events and downstream gene expression are of interest.
THE INVENTIONUW–Madison researchers led by Prof. Helen Blackwell have developed novel inhibitors of LasR, a quorum sensing receptor, in P. aeruginosa. The compounds are analogs of V-06-018, an inhibitor described in the scientific literature in 2006. The potency and efficacy of the compounds – measured by IC50 and maximum inhibition, respectively – were determined to exceed the parent molecule and are the most potent inhibitors of their kind reported to date.
  • Prevention or treatment of P. aeruginosa infection
  • Potent (3µm IC50 for LasR inhibition)
  • Inhibit QS-related genes and phenotypes
  • Reduced susceptibility to active efflux in P. aeruginosa
  • Hydrolytic stability
  • Could decrease cost of treating bacterial infections involving biofilms, which exceeds $1 billion per year in the U.S.
STAGE OF DEVELOPMENTThe ability of the compounds to inhibit LasR activity was evaluated in a cell-based gene reporter assay.
Contact Information
For current licensing status, please contact Rafael Diaz at or 608-960-9847.
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