Bacillus anthracis can quickly transform from a dormant spore (the white powder sent to U.S. lawmakers and others in the mail in 2001) into an active, quickly-multiplying organism once it gets inside the warm lungs of a host. Bacillus anthracis can cause infection elsewhere in the body, but is most serious and potentially deadly when its spores are inhaled.
Bergmans team focused on the mystifying step in anthrax infection when the bacteria pass unrecognized inside macrophages, the primary immune cells able to kill most bacteria.
Somehow the bacterium avoids being killed and actually hijacks these phagocytes (microbe-killing cells), Bergman says. New drugs, he says, 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.
Once the bacteria reach the bloodstream, they become unrecognizable to immune cells there. At this stage, they cause death from septicemia in essentially all people infected. Even with modern ICU support, the mortality rate for infections that progress to this stage is greater than 50 percent.
To understand what happens in the anthrax microbe as it activates inside the defender macrophages, Bergmans team used DNA microarrays, a technology emerging in the last decade, to examine mouse macrophage cells infected with the attenuated version of the microbe. It is modified so that it cannot infect laboratory workers but remains infectious in mice and other animals. The form is also used in animal anthrax vaccines.
The scientists 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. They identified seve
|Contact: Anne Rueter|
University of Michigan