Scientists Build a 3-D Model to Better Understand Anthrax Infections

A team of researchers just pieced together a three-dimensional map of Bacillus anthracis, the bacteria that cause potentially deadly anthrax infections. The findings are helping scientists understand how the bacterium transfers toxins into cells. The details are in a paper that was just published in The Journal of General Physiology.

Anthrax infections are caused by Bacillus anthracis and spread through spores produced by the bacteria. The people at greatest risk of infection are those who work with animals. Livestock and other animals are more likely to harbor the bacteria than humans. In some cases, a person can become infected by breathing in the spores. Symptoms vary and can change based on the route of infection but skin ulcers are common. Anthrax is extremely rare in the United States but cases regularly pop up in Africa, southern Europe, and southern Asia. B. anthracis bacteria are sometimes used as biological weapons. Infections are serious and fatal if not quickly treated.

Researchers used a technique called cryo–electron microscopy to calculate a three-dimensional map of the prepore complex form of anthrax. The prepore complex consists of enzymes called lethal factor (LF) and edema factor (EF) plus the protective antigen protein (PA). Together, these enzymes and proteins make up the anthrax toxin.

The team found that seven or eight PA proteins would first form a pore in the cell membrane. Toxic LF and EF molecules could then flow into the cytosol of the cell. Both LF and EF must unfold in order to pass through the pore, however, folding back up once inside. Interactions between LF molecules helped regulate the folding and as each LF entered the pore, the next molecule would be destabilized and primed to enter. This resulted in a “conveyer belt” of toxins constantly entering the cell.

Three-dimensional models are helping researchers understand how complex molecules function. The findings of this study provide new insights into the mechanisms that allow anthrax to translocate toxins into cells.

REFERENCE

Lucien Fabre et al. Structure of anthrax lethal toxin prepore complex suggests a pathway for efficient cell entry. The Journal of General Physiology (2016).

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