UIC receives federal contract to develop antibiotics against three bacterial infections

Researchers at the University of Illinois at Chicago's Center for Pharmaceutical Biotechnology have been awarded a federal contract for up to $13.8 million to develop antibiotics to treat anthrax, tularemia and plague.

The five-year contract is from the Defense Threat Reduction Agency, the U.S. Department of Defense's combat-support agency for countering weapons of mass destruction.

The three diseases are caused by naturally occurring bacteria classified as "category-A" agents that could be used in bioterrorism and biowarfare.

Anthrax infection can occur by absorption through the skin, by inhalation, or through the gastrointestinal tract. If left untreated, the disease can be fatal. Tularemia, or rabbit fever, has a low fatality rate if treated, but it can be incapacitating. It can be contracted through contact, inhalation, ingestion of contaminated water, or by insect bites.

Plague is caused by a bacterium found in rodents and their fleas in many areas of the world. The typical sign of the most common form of human plague is a swollen and tender lymph gland, accompanied by pain.

Bioweapons derived from bacteria can be a serious danger to military personnel and civilians, says Michael Johnson, professor emeritus and lead researcher on the contract. The microorganisms pose a risk to national security because they can be easily disseminated, result in high mortality, and have a potentially major public health impact.

Some strains of anthrax are resistant to antibiotic drugs. Such strains could be chosen or engineered as bioweapons to kill or incapacitate humans because drug-resistant infections would be very difficult to treat, Johnson said.

"New antibiotics targeting resistance are strongly needed," Johnson said. "However, the pharmaceutical industry has largely abandoned antibiotic research. There are few antibiotics in the development pipeline, and most of those in development target currently established mechanisms of action, potentially making them immediately susceptible to drug resistance."

Resistance arises partly because most antibiotics target the "active site" of a single enzyme, where even a single genetic mutation can lead to antibiotic resistance, Johnson said. Recent studies suggest that drugs that act on multiple biological targets may be more therapeutically robust.

Johnson and his research team recently discovered that bacterial survival depends on sequential enzymes in a certain biosynthetic pathway. Experiments on the microorganisms suggested those enzymes are attractive targets for novel broad-spectrum antibiotic development. The pathways are common to many so-called Gram-positive bacteria and other "category-B" biological agents such as brucella, salmonella and E. coli.

The methodology established in the research will also be applicable to drug discovery against other pathogenic targets, Johnson said.