Select Agent: Bacillus anthrasis, Pasteur Strain

Bacillus anthracis is a gram-positive, spore-forming bacterium that is the causative agent of anthrax (CDC 2020). Most commonly found in soil, B. anthracis causes anthrax via three modes of transmission: cutaneous, gastrointestinal, and inhalation. As CDC (2020) describes, cutaneous anthrax causes groups of blisters with swelling and itching. Those lesions turn into painless, black skin ulcers. This cutaneous form of anthrax is most common. Inhalation anthrax may lead to fever, chest pain, shortness of breath, dizziness, cough, vomiting, drenching sweats, and extreme tiredness. GI anthrax may also lead to fever, as well as bloody vomit and diarrhea, headache, flushing, fainting, and swelling of the abdomen (CDC, 2020). B. anthracis spores were weaponized in a series of bioterrorist attacks through the mail in 2001, prompting a swift and massive investment into bioterrorism preparedness by the US government (CDC, 2020).

B. anthracis has been around for decades. In the late 1870s, entire flocks of sheep were destroyed by severe anthrax. This caught the attention of the infamous Louis Pasteur, who used a heat attenuation technique to create an avirulent strain of anthrax that would later become the basis for the first successful anthrax vaccine (Mikesell et al., 1983). The heat-attenuated strain would later be known as the Pasteur strain, which is on the USDA Overlap List of Select Agents.

Why is the Pasteur strain on the list of select agents if it’s used to create vaccines?

Scorpio et al. (2006) describe two plasmids which provide virulence factors for B. anthracis. One plasmid (pX02) encodes the bacterial capsule that protects against phagocytosis in the host, and the other (pX01) encodes the disease-causing toxin. In order to cause disease, B. anthracis needs both plasmids. Pasteur’s heat attenuation inactivated pX01, the toxin-producing factor, which removed the bacterium’s ability cause disease  while retaining the pX02 capsule antigens necessary to mount an immune response (Scorpio et al., 2006). In the 1930s, a different strain of B. anthracis was discovered which had naturally lost its capsule plasmid – this strain is referred to as the Sterne strain and it is now the most commonly used strain for livestock immunization (CDC, 2022). Without the capsule plasmid, the Sterne strain has an excellent safety profile and is not included on the Overlap List of Select Agents.

The Pasteur strain of B. anthracis has been retained as a select agent to allow oversight of labs in which it may be combined with the Sterne strain to produce the virulent wild-type B. anthracis, accidental or otherwise (CDC, 2015). The possibility of de novo wild-type recombination comes with all the risks of the original, virulent B. anthracis.

References

Centers for Disease Control and Prevention. (2015). Possession, Use, and Transfer of Select Agents and Toxins: Biennial Review. Federal Register, 80(39). Retrieved from https://www.regulations.gov/document/CDC-2015-0006-0001

Centers for Disease Control and Prevention. (2020). Symptoms of Anthrax. Retrieved 4/22/23, from https://www.cdc.gov/anthrax/symptoms/index.html

Centers for Disease Control and Prevention. (2020). The Threat of an Anthrax Attack. Retrieved 4/22/23, from https://www.cdc.gov/anthrax/bioterrorism/threat.html

Centers for Disease Control and Prevention. (2022). Anthrax Sterne strain (34F2) of Bacillus anthracis. Retrieved 4/22/23, from https://www.cdc.gov/anthrax/resources/anthrax-sterne-strain.html

Mikesell, P., et al. (1983). Plasmids, Pasteur, and Anthrax. ASM News, 49(7). Retrieved from https://apps.dtic.mil/sti/pdfs/ADA138507.pdf

Scorpio, A., et al. (2006). Anthrax vaccines: Pasteur to the present. Cellular and Molecular Life Sciences, 63. DOI: 10.1007/s00018-006-6312-3