FDA study suggests critical potential role of individual bacteria in spreading anthrax through body

The spread of the most dangerous type of anthrax infection through the body slows down when the bacteria hit a temporary bottleneck created by the immune system, according to results of a study by scientists at the Food and Drug Administration (FDA). The bottleneck traps the bacteria until some of them escape and continue to spread the infection throughout the body.

The FDA finding suggests that potentially even a single anthrax bacterium that slips out of this bottleneck can continue to spread this type of anthrax, called inhalational anthrax, throughout the body. (The other types are gastrointestinal and cutaneous [skin] anthrax.)

Inhalational anthrax results from inhalation of spores (dormant forms of bacteria) into the nose and the tiny air sacs of the lungs, where special immune system cells engulf them and take them to lymph nodes (immune system tissues). From the lymph nodes they spread to other parts of the body.

Once inside the immune cells, the anthrax spores germinate (turn into the active form of bacteria) and multiply. The multiplying anthrax bacteria eventually break apart the immune cells and escape into the bloodstream, spreading to multiple organs and other lymph nodes. The spreading infection can eventually cause death if not treated successfully.

In order to track the spread of inhalational anthrax, the FDA scientists engineered three strains of the bacterium Bacillus anthracis Sterne, so that each of the three strains was tagged with a protein that emitted a different light visible to a special camera. These strains have little ability to cause disease in humans but can be lethal to the strain of mouse used in the study.

Despite giving mice equal numbers of each anthrax strain through inhalation into the lungs, the scientists found that, in the neck lymph nodes of any particular mouse, one of the three strains of anthrax was always dominant. Moreover, the dominant strain varied among the mice.

In addition, the organs subsequently infected by anthrax bacteria, such as the kidney, were always from that same, initially dominant strain.

This dominance of one strain occurred quickly in the neck lymph nodes and then continued as the infection spread from the lymph nodes to other organs in the body, such as the kidneys.

The findings of the FDA study suggest that dominant strains in the neck lymph nodes arose from replication of the first spore or active bacillus that succeeded in breaking though an immune system bottleneck. The potential for a single bacterium to escape the bottleneck and seed a new infection deeper in the body emphasizes the importance of preventing and detecting the initial infection caused by inhalation of anthrax spores, as well as the need for early treatment to block the spread of the bacteria to the bloodstream and then to multiple organs. Such early treatment might provide critical support to early immune system responses.

Title

“Dissemination Bottleneck in a Murine Model of Inhalational Anthrax”

Infection and Immunity

2012, 80 (9):3189

DOI: 10.1128/IAI.00515-12

Authors

Roger D. Plaut, Vanessa K. Kelly, Gloria M. Lee, Scott Stibitz, Tod J. Merkel

Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland