The ability of bacteria to communicate with each other through chemicals was first discovered in the early 1980s. Pathogenic bacteria use this system—so-called quorum sensing—to signal the start of the infection once they have reached a specific density. Several species-specific pathways leading to the release of such chemicals (called autoinducers; AI) were found, but it was not until a signaling system conserved among a range of pathogens—the AI-2 pathway—that researchers saw a means of harnessing quorum sensing for treating bacterial infections. Bonnie Bassler of Princeton University (Princeton, NJ) and Michael Surette of the University of Calgary (Calgary, Alberta, Canada), who discovered Al-1, founded Quorex Pharmaceuticals in early 1999, along with Jeffrey Stein, then principal scientist at Diversa (San Diego, CA), and Bob Robb, manager of a San Diego–based VC fund, BioVentures West. (Click here for company profile.)

Quorex owns proprietary technologies, gene sequences and proteins (including the AI-2 molecular structure) that may lead to the identification of new anti-infectives. These drugs are targeted at bacterial surface receptors, preventing them from recognizing autoinducer molecules. This then shuts down the communication pathway that leads to the expression of the pathogen's virulence factors. A secondary result (to be confirmed with additional animal studies) is that the drugs induce a bacteriostatic effect similar to that achieved with chloramphenicol, tetracycline, and erythromycin—the infecting bacteria are unable to obtain nutrients or produce growth factors within the host, and are therefore die or are eliminated by the host's immune system.

New weapons are needed in the fight against increasing drug resistance among pathogenic bacteria, caused by the over-use of traditional antibiotics. Quorex's quorum-sensing inhibitors could be used against a variety of pathogenic bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, E. coli O157:H7 (the cause of recent outbreaks of serious gastroenteritis), Haemophilus influenzae, and Helicobacter pylori. Moreover, because the AI-2 pathway is not prevalent in non-pathogenic bacteria, and is absent in higher organisms, drugs will be both more pathogen-specific and less toxic in humans. The company is also looking at non–quorum-sensing targets—newly discovered bacterial proteins that regulate apoptosis in their (mammalian) cell hosts. Bacterial cells control the cell suicide mechanisms of its host to enable their proliferation. This technology and target family was recently acquired from the Burnham Institute (La Jolla, CA).

Another company currently pursuing similar microbial targets is Aurora Biosciences, which acquired Quorum Sciences (Iowa City, IA) in October 2000. However, Quorex has succeeded in attracting an experienced drug development team, led by Krzyzstof Appelt, formerly of Agouron and responsible for the development and commercialization of its HIV drug, Viracept.