"A key aspect of anthrax spore biology concerns the germination process through which the dormant spore becomes a reproductive, disease-causing bacterium," explained Al Claiborne, Ph.D., the principal investigator. "The potential importance of such a germination control mechanism in anthrax is clear, as spore germination and outgrowth are fundamental to proliferation."
Claiborne, co-director of Wake Forest's Center for Structural Biology, added, "Basic understanding of the regulatory signals that promote germination will enable discoveries leading to drugs that block the process."
The research is being paid for by a $152,687 grant from the Southeast Regional Center of Excellence in Biodefense and Emerging Infections, based at Duke University, one of eight such regional centers funded by the National Institute of Allergy and Infectious Diseases.
The other institutions in Claiborne's project include a co-investigator at Virginia Tech and collaborators at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md, and the University of California, San Diego.
The research stems from lessons learned from studying the bacteria that cause Staphylococcus infections and two other bacteria in the same group as anthrax.
Claiborne said the group proposes that a vitamin B5 derivative known as Coenzyme A plays a crucial role in the germination of the anthrax spores. They have already shown that anthrax is missing a similar cofactor called glutathione that is common to many other bacteria, as well as humans.
The researchers are working with a non-pathogenic strain of anthrax. The genome sequences of four strains of the bacteria, known scientifically as Bacillus anthracis, have been determined.
The group also will be exploring the three-dimensional structures and the functions of the proteins involved. State-of-the-art facilities at the Center for Structural Biology will be used to determine how genetic information in the anthrax chromosome translates into a vast array of protein structures, Claiborne said. Once they know the structures, they may not only be able to provide new details on how anthrax develops, but also pick out structural vulnerabilities that are key to designing new therapeutic agents to prevent anthrax.
Interest in determining how to stop anthrax remains high, not only after the 2001 attacks through the mail that resulted in 18 cases and five deaths, but also after the recent scare at two military mailroom facilities when anthrax alarms went off.
The group also would like to understand another closely related bacterium, Bacillus cereus, one strain of which can produce anthrax-like symptoms.
The research team includes Conn Mallett, Ph.D., Derek Parsonage, Ph.D., graduate students Carleitta Paige, Jamie Wallen, and Tim Colussi, and senior research assistants Bill Boles, M.S., and Sumana Choudhury, M.S. Paige earlier received a $161,000 graduate fellowship from the Department of Homeland Security to support her research.