By Mary Welch
Quorum Sciences Inc. doesn't even have a name for its technology, but the Cystic Fibrosis Foundation is so intrigued with its antibacterial treatment that it awarded the two-year-old company almost $1 million to continue the development.
"I guess we should name it," said Stephen Turner, Quorum's chairman. "Right now we are optimizing our lead compound and expect to file an IND [investigational new drug] application in 2001."
Quorum's technology is based upon the work of Peter Greenberg, the company's chief scientific officer, co-founder, and a professor of microbiology at the University of Iowa. His technology is focused on disrupting the chemical signaling communications that occur between bacteria cells.
Traditional antibiotics effectively kill or block the growth of a wide spectrum of bacterial pathogens when they exist in a free-floating form inside the body. However, many infections, such as the Pseudomonas aeruginosa (PA) found in cystic fibrosis, actually live in a structured community of bacterial cells. These cells are wrapped up in a self-produced polymeric matrix that adheres to a surface. In the case of cystic fibrosis, that surface is the lung, and this structured society of cells, called a biofilm, lands and sticks to the lungs of more than 80 percent of cystic fibrosis patients.
Biofilms play an important role in several medical conditions, such as kidney stones, chronic ear and urinary-tract infections, and gum disease. In fact, the Centers for Disease Control and Prevention said biofilms - also known as bacterial scum - are involved in 65 percent of all human bacterial infections.
At first the biofilm is just a layer of cells attached to a surface. However, as the cells multiply, they start sending signals to each other and reorganize into a pattern of pillars and mushroom-shaped structures, all connected by channels that deliver food and remove waste. Essentially, they become a communal organization with its own defense capabilities and communication systems.
"These bacteria are the basis for almost every disease, and they form a matrix," Turner said. "They are impossible to kill, which gets us to cystic fibrosis. Once these cells get established, they never go away and they start communicating with each other through signaling cells. But if you create a drug that blocks those signals, you can keep the biofilm from forming and the cells become susceptible to antibodies."
Greenberg and his team identified a substance that triggers the biofilm formation in PA. This substance, belonging to a class called lactones, prompts more than 40 genetic changes that tell these single microbes to remodel their cell walls and begin spitting out slime.
Using its proprietary technology for identifying inhibitors of bacterial signaling, Quorum has developed novel antibacterial drugs for use in the treatment of PA infections in cystic fibrosis. Essentially, Quorum's solution is to develop drugs that tell the cells not to band together and form into the tough-to-fight biofilm. As free-floating single cells, they again should be more vulnerable to antibiotics.
"We believe that inhibition of bacterial signaling should render PA more susceptible to treatment, either directly through the immune response system or in combination with traditional antibacterial agents," Turner said. "It's a neat and fundamental way of opening up the possibility of preventing infections. It's a new way to think of antibacterial solutions."
As it is proving its theory and technology in the preclinical stage, Quorum is looking beyond cystic fibrosis.
"Ninety percent of deaths occur because infections overwhelmed the patient," Turner said. "If you could develop other signal-blocking medicines that stop the communication in other bacterial infections, such as Escherichia coli and wound healing, then it's easier to prevent or treat other diseases as well. We're attacking a population of bacteria rather than the single cells. The synergistic effects of the antibiotics should improve their effectiveness."
Quorum got its start when Turner, at the Maryland Biotechnology Institute, heard about bacterial signaling and Greenberg's work. Turner had been involved in starting several biotech companies, including OncorMed Inc., of Gaithersburg, Md.; Clinomics Inc., of Frederick, Md.; and Bethesda Research Laboratories Inc.
"I thought it was pretty interesting and some $500,000 in angel investor money started us off," he said.
Since its founding, the company has formed contract research agreements with Warner-Lambert Co., of Morris Plains, N.J.; Cincinnati-based Procter & Gamble Co.; and the Center for Biofilm Engineering in Bozeman, Mont. It also has developed proprietary in vivo bacterial screens for identifying signaling inhibitors to PA, and screened compound libraries. In addition, it has identified several chemical compounds and classes of inhibitors of bacterial cell signaling in PA. Quorum maintains its headquarters in Frederick, Md., but has its research operations in Iowa City, Iowa.