Understanding the Anthrax Threat

A new study reveals how anthrax-causing bacteria survive and grow inside unwitting immune cells during the crucial first moments of anthrax infection.

Researchers at the University of Michigan Medical School (Ann Arbor, USA) conducted mouse studies using DNA microarray technology, and were able to track which genes and enzymes play key roles during the bacterium's infiltration into macrophages, the immune system's first-responder cells in the lungs. The researchers were able to profile all the significant genetic activities in the microbe at several points in time as it invaded the macrophage, germinated, killed its host, and then escaped to spread further. Among a large number of genes shown to be highly active, the scientists picked one to study further, a previously uncharacterized gene in the MarR family that possibly regulates transcription. When they infected mouse cells with a Bacillus anthracis strain altered to lack the gene, they found the bacteria were significantly less able to cause disease.

The researchers also identified several pathways and functions that helped the microbe survive and thrive, which could be targets for future drugs. The next step will be to screen compounds that could potentially block the action of this gene and other genes identified in the study. The study appears in the July 2007 issue of the journal Infection and Immunity.

"Somehow the bacterium avoids being killed and actually hijacks these phagocytes [microbe-killing cells],” said lead author Nicholas H. Bergman, Ph.D., a research assistant professor of Bioinformatics. "New drugs should target the bug during the brief window of vulnerability, when the bacteria transform from dormant spores into active, growing organisms. That chance exists for a few hours when the invaders are inside immune cells in the lung and then pass from the lungs to the lymph nodes.”

Anthrax is an acute infectious disease and is highly lethal in some forms. Anthrax is one of only few bacteria that can form long-lived spores. Anthrax, most commonly occurs in wild and domestic grass eating mammals, can also be caught by humans when they are exposed to dead infected animals, and can also and used as a biologic weapon. The word anthrax is derived from the Greek word anthrakis, or "coal,” in reference to the black skin lesions its victims develop in a cutaneous infection.


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