Washington University Licenses New Antibacterial Technology

SIGA Pharmaceuticals is a New York-based drug development companythat produces vaccines, antibiotics and novel anti-infectives. It alsosigned agreements with MedImmune and Astra, two biotech companies thatpreviously had licensed the technology from Washington University.

"We are delighted to enter into a relationship with this excitingnew biopharmaceutical venture," says P. Andrew Neighbour, Ph.D., theUniversity's associate vice chancellor and director for technologymanagement. "We are optimistic that SIGA will develop effective new drugsfor the treatment ofGram-negative bacterial infections using this technology."

The technology was developed by Scott J. Hultgren, Ph.D., associateprofessor of molecular microbiology at the School of Medicine. Over thepast decade, Hultgren's group has determined how Gram-negative bacteriamanufacture the structures that allow them to cling to human tissues andtherefore cause disease. Gram-negative bacteria have an outer lipid layerand do not take up Gram stains.Most of Hultgren's work has focused on strains of E. coli thatinfect the kidney and bladder. But the same principles apply to many otherpathogens, including those that cause middle-ear infections, pneumonia,meningitis and gonorrhea.

"The knowledge that we generated by studying thestructure and function of microbial attachment has provided a blueprint forthe 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 kidneyor bladder lining like keys into locks. Firmly anchored, the bacteria goabout their business undisturbed.Hultgren's team has identified the major components along the pilusassembly line. They include a protein that chaperones pilus subunits to theouter bacterial membrane and another that extrudes them to the cellsurface. The researchers also have identified compounds that may inhibitone of these proteins. With the SIGA funding, they now will develop andtest additional compounds. Such drugs should prevent Gram-negativepathogenic bacteria from making pili. The bald bacteria would be unable tocause disease.

"The mode of action of this new class of anti-infectives will beunlike any other previously discovered," Hultgren says. "This willcircumvent the resistance mechanisms already established in manyGram-negative bacteria. And because the pathway that makes pili isconserved in these microbes, inhibitors discovered by the SIGA/WashingtonUniversity collaboration have the potential to bebroad-spectrum antibiotics."