Scientists Learn How Anthrax Creates Its Infectious Spores

In the age-old battle between man and microbe, it pays to know your enemy. This is especially true for Bacillus anthracis, the bacterium that causes anthrax. Tiny spores of this highly infectious pathogen can survive drought, bitter cold, and other harsh conditions for decades, yet still germinate almost instantly to infect and kill once inside an animal or human host.

In a collaboration funded by the U.S. Office of Naval Research and the National Institutes of Health, scientists from three major research institutions – the University of Michigan, The Institute for Genomic Research (TIGR), and The Scripps Research Institute – are working together to identify the genes and proteins involved in anthrax's deadly metamorphosis. Their work provides information other researchers can use to develop new vaccines and treatments targeted at specific points in the complex process of anthrax growth and spore formation.

The first results of the collaboration's work will be published as the cover story in the January 1, 2004 issue of the Journal of Bacteriology and are currently posted on the journal's web site. This study is the first analysis of a bacterial pathogen using the combined investigative tools of genomics and proteomics. It is also the first study to document, at a molecular level, all the genes and proteins involved in B. anthracis spore formation.

"[The study] clearly demonstrates the benefits of combining genomics and proteomics in a single study," says Hongbin Liu, the paper's first author and a former Scripps Research postdoctoral fellow. "The combined approach helped deepen our understanding of the complexity of spore growth and sporulation."

Major findings of the study include:

• When compared to other bacteria, anthrax spore formation is an unusually complex and intricate process. Up to one-third of all the genes in the Bacillus anthracis genome are involved in spore production.

• Genes are expressed in five discrete phases over a five-hour time period.

• Each mature anthrax spore contains about 750 individual proteins.

The collaboration's scientists identified 2,090 B. anthracis genes, of nearly 6,000 in the entire genome, which appear to be involved in spore formation. Gene activity occurred in five overlapping waves spread across a five-hour time period, but actual construction of the spore didn't begin until the fourth wave of gene expression.

Complete data from the collaboration's study of the genome and proteome of B. anthracis spores has been posted on the National Center for Biotechnology Information's Gene Expression Omnibus database at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?dg=geo., where it will be freely available to the scientific community. While the data will be extremely valuable to biomedical researchers, it has no value related to the use of anthrax as a biological weapon.

The article, "Formation and Composition of the Bacillus anthracis Endospore," was authored by Hongbin Liu, Nicholas H. Bergman, Brendan Thomason, Shamira Shallom, Alyson Hazen, Joseph Crossno, David A. Rasko, Jacques Ravel, Timothy D. Read, Scott N. Peterson, John Yates, III, and Philip C. Hanna. It appears in the Journal of Bacteriology, Vol.186, pp. 164-178, Jan. 2004 and is posted online at: http://jb.asm.org/content/vol186/issue1/index.shtml?etoc.

 

 


This colorized TEM image of an anthrax spore, magnified 92,000 times, shows layers of the spore's tough outer coat surrounded by the balloon-like exosporium. Photo credit: Brendan Thomason and Philip Hanna, University of Michigan Medical School. Used with permission from the Journal of Bacteriology.