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University of Illinois at Chicago receives $15.7 million grant to stop anthrax

University of Illinois at Chicago

A team of ten researchers at the University of Illinois at Chicago has received a $15.7 million grant for a multi-pronged program to develop drugs to treat and stop the spread of anthrax, the often fatal infectious disease that has been rated second to smallpox in potential impact as an agent of bioterrorism.

The grant is the largest ever received at UIC.

Anthrax is a serious threat because it can be bioengineered to be resistant to multiple drugs. The primary goal of the UIC program is to search for new drugs that will provide alternate defenses against an engineered organism.

Michael Johnson, professor and director of the UIC College of Pharmacy's Center for Pharmaceutical Biotechnology, will direct the four-and-a-half-year program, which is funded by the National Institute of Allergy and Infectious Diseases, one of the National Institutes of Health.

Research will be conducted simultaneously in five interrelated projects that build on a well-established collaborative network of UIC researchers in the colleges of pharmacy and medicine.

The program integrates multiple strategies toward the development of new antimicrobials, new potentiators of existing antimicrobials and direct inhibitors of the anthrax toxin as strategies to combat natural and bioengineered forms of Bacillus anthracis.

Johnson said it is technically quite feasible for terrorists to develop new, more potent strains of B. anthracis that could be a substantial threat in future attacks. Well before the anthrax attacks of 2001, anthrax was identified by the Working Group on Civilian Biodefense as one of the most serious organisms -- capable of causing disease and deaths in sufficient numbers to cripple a city or region.

Experts estimate that release of aerosolized anthrax spores could result in tens of thousands of deaths, Johnson said.

While the anthrax strain unleashed in 2001 was susceptible to conventional antibiotics, Alex Neyfakh, UIC professor of medicinal chemistry and pharmacognosy and principle investigator for one of the grant projects, has shown that anthrax can be selected for resistance to ciprofloxicin, the current drug of choice.

This demonstrates, Johnson said, that drug-resistant strains can be isolated or engineered without great difficulty.

"The damage that could be done with a strain of B. anthracis that had been bioengineered to be more potent and to incorporate additional virulence factors that could accelerate its pathology and erase vaccine-conferred immunity is truly terrifying," he said.

While stopping the threat of anthrax is a national priority, it does not have the commercial potential to be a prime development area for the pharmaceutical industry, Johnson said. But in the academic setting at UIC, he said, "the breadth of expertise will allow us collectively to pursue therapeutic development across the full spectrum, from target identification to in vivo evaluation."

His collaborators' areas of expertise include bacterial genetics and biochemistry, structural biology of macromolecules, computer-assisted drug design, synthetic chemistry, macrophage biology, animal modeling and clinical infectious disease.

The five interrelated projects will address different aspects of the search for novel therapeutic agents to defend against engineered organisms.

Project one will identify and validate new antibiotic targets in ribosomal RNA. Alexander Mankin, professor of medicinal chemistry and pharmacognosy, is project leader.

Project two, led by Neyfakh, will identify and validate new infection-related targets in B. anthracis.

Project three, led by Johnson, will use structure-based design and high throughput screening to develop lead inhibitors of currently known and yet-to-be-identified antibiotic targets.

Project four will develop inhibitors to prevent the binding of the B. anthracis toxin to the cellular receptor. Michael Caffrey, assistant professor of biochemistry and molecular genetics, is project leader.

Project five will evaluate the role of antibiotics in modulating cytokine activation and toxin triggering following macrophage infection and animal model development. Dr. James Cook, chief of infectious diseases at UIC, is project leader.


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