Protein Toxins Help Anthrax Avoid Immune System

In a recent study, researchers found a protein complex (lethal toxin, or LT) produced by Bacillus anthracis, the bacteria that causes anthrax, that is able to inhibit and destroy macrophages, the immune system's primary defense against such pathogens. The study was published August 29, 2002, in the online journal Science Express.

Instead of being destroyed by the immune system, the anthrax bacteria survive and germinate within the macrophages and travel with them throughout the body to the lymph nodes, and eventually into the bloodstream, ultimately leading to fatal systemic shock if treatment fails.

The investigators, from the University of California, San Diego (UCSD, USA), looked for the mechanism used by the bacteria to evade destruction by the macrophages. They found that the bacteria manufacture a number of proteins that work together to disrupt macrophage function.

Another protein, called protective antigen (PA), binds to the cell surface and allows bacterial proteins to penetrate the macrophage. These proteins, termed lethal factor (LF), cleave and disable specific protein kinases (called mitogen activated protein kinase kinases, or MKKs) that play a vital role in activation of the p38 protein kinase, whose enzymatic activity is essential for survival of the macrophage. The authors of the current study believe that PA and LF function together in the form of LT, which inhibits p38. Inactivation of p38 leads to the death of the macrophage and prevents secretion of the chemokines and cytokines that would alert the immune system to the presence of an invading pathogen.

Dr. Michael Karin, professor of pharmacology at UCSD and the study's senior author, explained that anthrax and other deadly pathogens, such as bubonic plague, take several days or up to a week for symptoms to appear, as the body's normal immune response has been subdued. "We have wondered why this bug does not make patients sick early on, especially since it does not take many bacteria to make us sick. Feeling sick is actually good. It means we are fighting the effects of infection with a fever or runny nose. Not being sick means your immune system is not detecting the infection.”



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