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$14M project to develop antibiotics against biowarfare

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Michael Johnson

Michael Johnson with co-investigator Hyun-Young Jeong: "New antibiotics targeting resistance are strongly needed."

Photo: Roberta Dupuis-Devlin

Researchers in the Center for Pharmaceutical Biotechnology received a federal contract for nearly $14 million to develop antibiotics to treat anthrax, tularemia and plague.

The five-year contract was awarded by 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 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.


Serious danger

Bioweapons derived from bacteria can be a serious danger to military personnel and civilians, said 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, he explained.

Some strains of anthrax are resistant to antibiotic drugs. Used as bioweapons to kill or incapacitate humans, these drug-resistant infections would be very difficult to treat, Johnson said.

"New antibiotics targeting resistance are strongly needed," he 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.


Bacterial survival

Recent studies suggest that drugs that act on multiple biological targets may be more effective.

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 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 developed in the research can be used to create drugs against other pathogenic targets, Johnson said.

Johnson's UIC collaborators include James Cook, professor of medicine, Leslie Fung, professor of chemistry, and Hyun-Young Jeong, assistant professor of pharmacy practice.
Collaborators at Purdue University are organic chemist Arun Ghosh, formerly of UIC, and biochemist T. Joseph Kappock.


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