A Quarterly Publication of City of Hope | Volume 18 Number 3 | Summer 2007
The culprit is Clostridium botulinum, a tiny organism that produces botulinum toxin. When ingested, the toxin causes paralysis and even death. Now, City of Hope scientists have developed a wayto detect this poison that could not only improve food safety, but also potentially protect transplant patients from deadly fungal infections and the public from bioterrorism.
Markus Kalkum, Ph.D., assistant professor in the Department of Immunology, and Karine Bagramyan, Ph.D., a research fellow in the department, devised a new method that detects the toxin in an array of substances including food products.
photo: Darrin S. JoyMarkus Kalkum and Karine Bagramyan
Botulism normally results when a person eats food tainted with C. botulinum bacteria or if the bacteria enter a wound. Infants also are susceptible if bacteria gain a foothold in their intestinal tract.
In addition, government agencies indicate that botulinum toxin may be a tool in a potential terrorist attack. The poisonis so potent, just one gram could kill more than a million people, according to a 2001 study in the Journal of the American Medical Association.
The new test is less expensive, faster and easier to perform than the current standard and, unlike the current standard, it does not require the use of mice for testing. Findings were published in the April 30, 2008 issue of PLoS ONE.
The new test can detect about 300 molecules of toxin in one milliliter’s worth of a sample, making the test 12,000 times more sensitive than today’s standard, said Kalkum. It can also test for botulinum in virtually any solution, making it more effective and flexible.
To create their test, the researchers bound antibodies against botulinum toxin to microscopic beads. Scientists can test a solution by mixing the beads into it letting the antibodies grab any toxin molecules floating about. The beads are then washed and exposed to special chemicals that glow under ultraviolet light when the botulinum toxin is present.
The scientists tested the assay by mixing botulinum toxin in a variety of substances, including milk, gelatin solutions and carrot juice.
They also successfully tested it using blood serum. That is encouraging because they want to adapt the technology for other uses such as testing transplant and other immune-compromised patients for fungal infections, which cost many of these patients their lives.
“I see no reason why we can’t adapt this technology to benefit transplant patients,” said Kalkum. The mechanism would be very similar, “and we’ve already been able to detect other biomolecules associated with fungal infection,” Kalkum said.
In addition, the test could be used to better understand how the human body reacts to and metabolizes medicines such as Botox, making cosmetic drugs safer, according to Kalkum.
The research was funded under the auspices of the Pacific Southwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, one of 10 centers that support the National Institute of Allergy and Infectious Diseases’ Biodefense and Emerging Infectious Diseases Research Agenda. The center will support research on an automated device that uses the new test.