Scientists from the Max Planck Institute for Infection Biology in Berlin discovered why lung, but not skin, anthrax infections are lethal. As reported in the newest issue of PloS Pathogen (November 2005) Neutrophils, a form of white blood cells, play a key role in anthrax infections. They can kill Bacillus anthracis by producing a protein called alpha-defensin. This discovery might now pave the way towards the development of new therapies for the fatal lung form of anthrax.
Bacillus anthracis is the causative agent of anthrax. What makes Bacillus anthracis especially dangerous is that these bacteria can form spores. The spores are extremely resistant against environmental stress and can survive for years. Infection with Bacillus anthracis can take place either via the lung or through the skin. Interestingly, the lung form of anthrax is almost always fatal, whereas skin infections remain localized and are rarely lethal. In contrast to the lung form, the skin form of anthrax can be treated without problems and most patients recover.
During the past few years, Bacillus anthracis has also been used as a weapon for bioterrorism. Anthrax spores were sent in envelopes and inhaled and resulted in the death of 5 people in the USA.
The findings of the lab of Arturo Zychlinsky now help clarifying why the skin form is harmless in contrast to the lung form. After a skin infection with Bacillus anthracis, neutrophils are recruited to the site of infection. Neutrophils are white blood cells that can identify and kill microbes. In the skin, neutrophils take up the spores, which germinate inside the neutrophil to a vegetative (“growing”) bacterium. This vegetative bacterium is then attacked and killed within the neutrophil. The scientists succeeded in identifying the substance responsible for the killing of the bacteria. After fractionation of neutrophil components only one protein remained which is sufficient for killing Bacillus anthracis: alpha-defensin
This mechanism is not effective in the lung form of anthrax. Here, the number of neutrophils recruited to the site of infection is known to be low, and insufficient to kill bacteria. Thus, inhaled spores can germinate and spread through the organism. The scientists in Berlin now hope that their discovery will help to develop new drugs against the lung form of anthrax. There might be the possibility that the inhalation of alpha-defensin might kill vegetative bacteria in the lung and prevent dissemination.
Original work: PLoS Pathogen 1(3), November 2005