Yersinia murine toxin (Ymt)
Background and History:
Three major pandemics:
The Justinian Plague
The Black Death
Chinese Plague
Use as Bioweapon
Contraction of Y. pestis can be from
- Yersinia pestis is a lactose nonfermenter, urease and indole negative Enterobacteria.
- Y. pestis is an example of a category A bioterrorism agent. [4]
Three major pandemics:
The Justinian Plague
- Around Mediterranean Sea in 6th century, 50-60% of population died.
- Biovar: Antiqua
The Black Death
- Europe in 14th century, one-third of population died.
- Biovar: Medievalis
Chinese Plague
- China in 19th century, spread throughout world. 12 million people in China and India dead.
- Biovar: Orientalis
Use as Bioweapon
- In WWII, the Japanese army dropped plague-containing fleas in populated areas of China
- The United States and the Soviet Union developed techniques to aerosolize the plague after WWII [4]
Contraction of Y. pestis can be from
- Infected flea bites
- Eating infected animals like guinea pigs or camels
- Handling infected cats
- Human to human with airborne pneumonic plague
Mechanism:
- Yersinia murine toxin (Ymt) uses water to form phosphoenzymes to break down proteins in flea cells (Fig 1)
- The infected flea bites the human and Y. pestis is put into the host past the skin barrier.
- Most of the bacterium are killed by neutrophils at the bite site, but some will infect macrophages by utilizing a specific surface associated molecule via phagocytosis.
- Y. pestis survives inside macrophages and follow it during proliferation.
- Y. pestis will express virulence markers inside the macrophage such as Yops, F1 antigen, and V antigen (Fig 2)
- These markers will cause the macrophage to go through apoptosis, which will reduce proinflammatory cytokines, thus decreasing the amount of neutrophils.
- A capsule is formed around the bacterium before apoptosis of the macrophage, allowing the Y. pestis to survive as a non-foreign substance extracellularly.
- By controlling cytokine distribution, Y. pestis suppresses both B and T cell development throughout the body, as well as subverting phagocytosis to destroy other cells. [1] [2]
Signs and Symptoms:
Bubonic plague
Meningeal plague
Pharyngeal plague
Septicemic plague
Treatment:
Any person suspected of plague are kept in strict isolation for 48-72 hours after antibiotics are given. Patients are kept in quarantined until signs of pneumonia are gone and a sputum culture comes back negative for Y. pestis.
All cases of plague have to be reported to the local health department and the World Health Organization.
Citations
[1] Li, B., & Yang, R. (2008). Interaction Between Yersinia Pestis And The Host Immune System. Infection and Immunity, 1804-1811.
[2] Hinnebusch, B., Rudolph, A., Cherepanov, P., Dixon, J., Schwan, T., & Forsberg, A. (2002). Role of Yersinia Murine Toxin in Survival of Yersinia pestis in the Midgut of the Flea Vector. Science, 733-735.
[3] Wyangankar, S. (2014). Plague . Retrieved April 14, 2015, from http://emedicine.medscape.com/article/235627-overview
[4] Inglesby, T. (2000). Plague as a Biological Weapon: Medical and Public Health Management. JAMA: The Journal of the American Medical Association, 2281-2290
Bubonic plague
- High fever, chills, headache, body aches, extreme exhaustion, weakness, abdominal pain, and diarrhea
Meningeal plague
- Headache and nuchal rigidity.
- Buboes form.
Pharyngeal plague
- Sore throat, fever, and chills. Usually with cough, chest pain, dyspnea, purulent sputum or hemoplysis.
- Buboes can form
Septicemic plague
- Nausea, vomiting, abdominal pain, and diarrhea
- Toxic appearance and moribundity are apparent [3]
Treatment:
Any person suspected of plague are kept in strict isolation for 48-72 hours after antibiotics are given. Patients are kept in quarantined until signs of pneumonia are gone and a sputum culture comes back negative for Y. pestis.
All cases of plague have to be reported to the local health department and the World Health Organization.
- Hemodynamic monitoring and ventilatory support can be necessary
- Intraveneous fluids, epinephrine, and dopamine are used for dehydration
- 7-day course of oral doxycycline and ciproflaxin (sometimes chloramphenicol)
- Levoloaxin is usually prescribed for 10-14 days for either treatment or postexposure prophylaxis
- Buboes must be removed surgically if enlarged [3]
Citations
[1] Li, B., & Yang, R. (2008). Interaction Between Yersinia Pestis And The Host Immune System. Infection and Immunity, 1804-1811.
[2] Hinnebusch, B., Rudolph, A., Cherepanov, P., Dixon, J., Schwan, T., & Forsberg, A. (2002). Role of Yersinia Murine Toxin in Survival of Yersinia pestis in the Midgut of the Flea Vector. Science, 733-735.
[3] Wyangankar, S. (2014). Plague . Retrieved April 14, 2015, from http://emedicine.medscape.com/article/235627-overview
[4] Inglesby, T. (2000). Plague as a Biological Weapon: Medical and Public Health Management. JAMA: The Journal of the American Medical Association, 2281-2290