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Plague (Yersinia pestis) Biomedical Mechanics

The bacterium that causes plague, Yersinia pestis, is primarily a rodent pathogen. Scientists believe the Yersinia pestis bacteria evolved three plasmids of genetic coding 20,000 years ago that are essential for the transmission and virulence of the bacteria. Two of the plasmids, pMT1 and pPCP1, are unique to the Yersinia pestis bacteria and not seen in other Yersinia bacteria.

The Xenopsylla cheopis, the oriental rat flea, or Pulex irritans, the human flea, transmits plague from rodent to humans and other mammals. Two genetic expressions located on a pMT1 plasmid in the Yersinia pestis bacteria are essential in the transmission process: the Ymt and the Hms. In order to utilize the flea as a transmission vector, the Yersinia pestis bacteria must successfully colonize in the flea's gut. Scientists have isolated the Yersinia murine toxin (Ymt), an encoded phspholipase D (PLD) located at the 100 kb locus of the plasmid. The Ymt prevents the flea's immune system from destroying the bacteria through cytotoxic digestion, and allows the bacteria to colonize.

Once ingested by the flea, the bacteria multiply in the flea's midgut and colonize on a valve that connects the flea's midgut to its esophagus. These cells then are surrounded by an extracellular matrix, and they block the flow of blood ingested by the flea into the midgut. The matrix is created by a haemin storage expression (Hms)-dependent extracellular polymer of N-acetyl glucosamine that allows the bacteria to stack. The Hms is expressed by temperature dependent genes located at the 102 kb locus of the Yersinia pestis pMT1 plasmid, and only manifests at 26 degrees Celsius, the body temperature of fleas, but not at 37 degrees Celsius. The blocked flea suffers from hunger caused by this blockade and increases in aggressiveness as the flea seeks to alleviate its hunger. This increased aggressiveness enhances transmission as the flea jumps from host to host in search of food. The bacteria is regurgitated and released into the bloodstream of the human or mammal when the flea attempts to ingest blood into its blocked digestive system. The disease spreads and the fleas die of dehydration or starvation. If the temperature of a flea is raised to 30 degrees or in Yersinia pestis hms mutants, the Hms would not be triggered and the flea would survive.

Another Yersinia pestis plasmid, the pPCP1, holds the Pla expression at the 10kb locus. The Pla or plasminogen activator triggers fibrinolysis, the prevention of the blood's ability to coagulation or clot. This breaks down the extracellular matrix and membrane of host cells and facilitates the host's inability to contain the bacteria at the site of infection. Bubonic plague depends on Pla for its virulence. A third plasmid pCD1 also facilitates the bacteria's virulence.

The sylvatic (zoonotic) cycle of plague transmission account for naturally occurring incidence of plague. Wild rodents and prairie dogs, natural carriers of Yersinia pestis, transmit the disease to other carriers through an infected flea. In some cases, the bacteria could be transmitted in contaminated soil. The bacteria are spread to humans through direct contact with the wild rodent or an infected flea. The urban cycle of transmission charts the Yersinia pestis' progression the disease as it becomes an epidemic. Fleas or direct contact with wild rodents transmit the disease to domestic rodents. Domestic rodents transmit the disease to each other and to humans.

Yersinia pestis first manifests itself in the human population as bubonic plague. Upon entry through a flea bite, the human immune system kills most bacteria through polymorphonuclear leukocytes but a few survive. The survivors are engulfed by macrophages. Macrophages not only are unable to kill the bacteria but provide a protected shell in which the bacteria increase its virulence. In the 37 degree Celsius human blood, the bacteria encode the Yesinia Outer membrane Proteins (Yop) and Yersinia SeCretion (Ysc) located at 70 kb of the pCD1 plasmid. These expressions form a membrane around the bacteria to protect it against immune responses. Once developed, the bacteria kill the macrophages and spreads to the lymph nodes where they cause the swollen buboes that characterize the disease.

From the lymph nodes, the bacteria enter the bloodstream. The disease becomes septic plague that could lead to circulatory collapse and internal hemorrhaging. The bacteria may spread into the central nervous system; historical chronicles have recorded irrational behavior in plague victims such as dancing on the roof before dying of the disease. The bacteria may also enter the lungs and bacteria pneumonia may develop. Each cough expels the bacteria into the air. In urban environments of overcrowding, the pneumonic form of the disease develops to become airborne with a fatality rate of close to 100% if left untreated.




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