Bacterial Virulence Compound

About

Overview Many 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 Invention The 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. Applications New antibacterial compositions, coatings and packaging to control P. aeruginosa infections (e.g., treating cystic fibrosis patients) and potentially other pathogens. Key Benefits Novel combination strategy Utilizes two known small molecules Stage of Development The 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.