St. Louis, Feb. 11, 1998 -- Washington University in St. Louis has signed an agreement with SIGA Pharmaceuticals Inc. that gives the company exclusive rights to new antibacterial technology. The agreement will allow SIGA to develop an entirely new class of antibiotics that are less likely to be sidelined by bacterial resistance than current therapies. It also provides three years of research funding to the Washington University scientists who are involved in this project.
SIGA Pharmaceuticals is a New York-based drug development company that produces vaccines, antibiotics and novel anti-infectives. It also signed agreements with MedImmune and Astra, two biotech companies that previously had licensed the technology from Washington University.
"We are delighted to enter into a relationship with this exciting new biopharmaceutical venture," says P. Andrew Neighbour, Ph.D., the University's associate vice chancellor and director for technology management. "We are optimistic that SIGA will develop effective new drugs for the treatment of Gram-negative bacterial infections using this technology."
The technology was developed by Scott J. Hultgren, Ph.D., associate professor of molecular microbiology at the School of Medicine. Over the past decade, Hultgren's group has determined how Gram-negative bacteria manufacture the structures that allow them to cling to human tissues and therefore cause disease. Gram-negative bacteria have an outer lipid layer and do not take up Gram stains.
Most of Hultgren's work has focused on strains of E. coli that infect the kidney and bladder. But the same principles apply to many other pathogens, including those that cause middle-ear infections, pneumonia, meningitis and gonorrhea. "The knowledge that we generated by studying the structure and function of microbial attachment has provided a blueprint for the development of novel antimicrobial therapeutics and strategies," Hultgren says.
E. coli is covered with hair-like structures called pili. The tips of the pili carry proteins that fit into receptors in the kidney or bladder lining like keys into locks. Firmly anchored, the bacteria go about their business undisturbed.
Hultgren's team has identified the major components along the pilus assembly line. They include a protein that chaperones pilus subunits to the outer bacterial membrane and another that extrudes them to the cell surface. The researchers also have identified compounds that may inhibit one of these proteins. With the SIGA funding, they now will develop and test additional compounds. Such drugs should prevent Gram-negative pathogenic bacteria from making pili. The bald bacteria would be unable to cause disease.
"The mode of action of this new class of anti-infectives will be unlike any other previously discovered," Hultgren says. "This will circumvent the resistance mechanisms already established in many Gram-negative bacteria. And because the pathway that makes pili is conserved in these microbes, inhibitors discovered by the SIGA/Washington University collaboration have the potential to be broad-spectrum antibiotics." Editor's note: Hultgren's group also has developed a potential vaccine against uropathogenic E. coli. Last year, MedImmune demonstrated that the vaccine is effective in mice.