WARF: P160176US02

Compound Combination Targets Bacterial Virulence


Helen Blackwell, Michael Welsh

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing small molecule cocktails shown to be more effective than single compounds at inhibiting quorum sensing in P. aeruginosa and other bacteria.
OVERVIEWMany common bacterial pathogens delay virulence factor production until there is a sufficient number of cells that – working together – can overwhelm a host’s defense. To coordinate such an attack, some species use a method of cellular communication called quorum sensing (QS). Because of this association with virulence, QS systems are promising antivirulence targets and compounds capable of inhibiting QS are being investigated to fight dangerous bacteria.

A prime example is Pseudomonas aeruginosa, a highly adaptable species that commonly affects immunocompromised patients (e.g., those suffering from HIV, burns or chronic wounds) and is the leading cause of hospital-acquired pneumonia. It uses three independent QS systems (Las, Rhl, Pqs) to establish and maintain infection. Up to this point, strategies to block QS in this bacterium have targeted only one system at a time.

UW–Madison researchers have found that this singular approach is often ineffective in the type of nutrient-deficient environments (esp. low iron and phosphate) characteristic of human infections.
THE INVENTIONThe researchers have discovered that two lead compounds (E22/M64) can be combined to target multiple QS pathways at the same time (Rhl/Pqs), resulting in enhanced activity against P. aeruginosa and potentially other pathogens. This new cocktail approach is superior because it attenuates virulence factor production across a range of relevant environments where single compounds fail.
  • New antibacterial compositions, coatings and packaging to control P. aeruginosa infections (e.g., treating cystic fibrosis patients) and potentially other pathogens
  • Novel combination strategy
  • Utilizes two known small molecules
STAGE OF DEVELOPMENTThe researchers used chemical probes to evaluate the contribution of each QS pathway to virulence in wild-type P. aeruginosa under defined environmental conditions. The results indicate that two of the pathways (Rhl and Pqs) drive virulence factor production in phosphate- and iron-limiting environments. From this they produced a cocktail comprising E22/M64 and demonstrated attenuated virulence in environments where other inhibitors fail.
For More Information About the Inventors
Related Technologies
  • Welsh M.A., Eibergen N.R., Moore J.D. and Blackwell H.E. 2015. Small Molecule Disruption of Quorum Sensing Cross-Regulation in Pseudomonas aeruginosa Causes Major and Unexpected Alterations to Virulence Phenotypes. J Am Chem Soc. 137, 1510-1519.
Contact Information
For current licensing status, please contact Rafael Diaz at or 608-960-9847.
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