Anthrax Spores Use Failsafe Germination System

John Ireland and Philip Hanna Photo: Bill Wood

Protected by a tough outer coat that is impervious to cold, heat, drought and harsh chemicals, anthrax spores can remain dormant in the soil for decades. Once inside a living host, however, they can shed that coat, germinate and begin infecting cells in as little as 10 minutes.

Scientists know very little about what triggers an anthrax spore to break dormancy. Identifying the biochemical signals that start the process is an important first step in preventing anthrax infection.

A study by Medical School scientists John A.W. Ireland, Ph.D., and Philip C. Hanna, Ph.D., shows that germination requires the coordinated activity of several genes, receptor proteins and amino acids in at least two simultaneous signaling pathways. The U-M study, published in the March 2002 issue of the Journal of Bacteriology, is the first to match anthrax genes with specific amino acids and signaling pathways that trigger germination.
“Anthrax doesn’t rely on a single signal,” says Hanna, an assistant professor of microbiology and immunology. “Spores have a redundant germination mechanism. It’s the bug’s way of ensuring that it won’t lose its protective armor until conditions are right for germination.”

Hanna and Ireland discovered that amino acids, the fundamental building blocks of all proteins in the body, in combination with purine ribonucleosides, the building blocks of DNA and RNA, are triggers for anthrax spore germination. The process appears to begin when receptor proteins on the spore’s membrane bind to ring-shaped or aromatic structures found on certain amino acids and ribonucleosides.

“The receptor protein is the lock and ring structures are the keys,” says Ireland, a U-M post-doctoral research fellow.

“The only place we know where all the required elements for germination are present is inside our cells, especially our phagocytes — the scavenger cells of the immune system,” Ireland explains. “But even in the macrophage, where conditions are perfect for germination, the spore stays intact until at least two separate signaling pathways are activated.”

Because it can be handled safely outside a high-level bio-containment laboratory, Hanna and Ireland used Sterne-based strains of anthrax in their research. The Sterne strain has been altered, so it cannot infect people.

In future research, Hanna will test the amino acids and ribonucleosides to see if they trigger anthrax spore germination in tissue cultures. Eventually, he hopes to expand the study to animal models. His research is supported by the National Institutes of Health and the Office of Naval Research.

—SFP

Full text of the published article is available on the American Society of Microbiology Web site:
http://jb.asm.org/cgi/content/abstract/184/5/1296

To learn more about Hanna’s research, go to:
www.med.umich.edu/microbio/faculty/hanna.html

To learn more about anthrax, see the U.S. Center for Disease Control Web site:
www.bt.cdc.gov