Yersinia pestis CO92
A Microbial Biorealm page on the genus Yersinia pestis CO92
Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales; Enterobacteriaceae; Yersinia; Yersinia pestis
Description and significance
Yersinia pestis was first discovered by a French-born Swiss bacteriologist named Alexander Yersin in 1894 (2). The Gram-negative bacterium Yersinia pestis CO92 is the causative agent of the systemic invasive infectious disease classically referred to as the plague and it has been responsible for human pandemics. It was the causative agent of the Black Death, or the bubonic plague. The Black Death is estimated to have killed 30 to 60 percent of Europe's population between 1348 and 1350 (1). The aftermath of the plague consisted of religious, economic and social upheaval. The population of Europe did not recover for nearly 150 years. The appearance of the disease caused by Yersinia pestis is often characterized by buboes, swollen lymph nodes in the groin, underarm, and neck. Y. pestis often leads to necrotic tissue that is black in color which is where the name the Black Death originated. It is a zoonotic disease and the animal reservoirs that carry Y. pestis are most often fleas and rodents(11). These animals can pass the bacteria onto humans directly or indirectly (9). The pathway for infection is described in detail in the ecology section. The specific strain of Yersinia pestis CO92 has been studied for its possible role in biological warfare. An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment (8). Y. pestis CO92 is a very dangerous bacteria and if used in biological warfare it could be catastrophic for the entire global population.
The complete genome sequence of Y. pestis strain CO92 consists of a 4.65-megabase chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve (10). Y. pestis is host to the plasmid pCD1. In addition, it also hosts two other plasmids, pPCP1 (also called pPla or pPst) and pMT1. Together, these plasmids, and a pathogenicity island called HPI, encode several proteins that cause the pathogenesis, for which Y. pestis is famous (7).
Cell structure, metabolism & life cycle
Yersinia pestis CO92 is a Gram-negative, rod shaped bacterium. Y. pestis CO92 has a slime layer that is heat labile. Labile cells are cells that constantly divide by entering and remaining in the cell cycle. When the Y. pestis CO92 is in a host, it is nonmotile. However without a host, Y. pestis CO92 is motile. Y. pestis CO 92 uses aerobic respiration and anaerobic fermentation to produce and consume hydrogen gas for energy (4). Y. pestis is so elusive to the host’s immune system because of its ability to suppress it. Y. pestis produces two anti-phagocytic antigens explained in greater detail in the section ecology. These antigens are both required for virulence and are only produced when the organism grows at 37 degrees celsius. This explains why fleas are one of the bacteria resevoirs due to its lower body temperature (Hinnebusch). An anti-F1 serology test can differentiate between different species of Yersinia, and Polymerase chain reaction (PCR) can be used to identify Y. pestis CO92 (9).
Ecology (including pathogenesis)
Most of the spreading occurs between rodents and fleas. Every infected animal can transmit the infection to humans through contact with skin tissue. Humans can also spread the bacteria to other humans through sneezing, coughing, or direct contact with infected tissue. In the United States, several species of rodents are thought to maintain Y. pestis (8). It is known that rodent populations will have a variable resistance, which could lead to a carrier status in some individuals (9). There is evidence that fleas from other mammals have a role in human plague outbreaks. Initial acquisition of Y. pestis by the vector occurs during flea feeding on an infected animal. Several proteins then contribute to the maintenance of the bacteria in the flea digestive tract, among them the hemin storage (Hms) system and Yersinia murine toxin (Ymt). it has been demonstrated that Ymt is important for the survival of Y. pestis in fleas. The Hms system plays an important role in the transmission of Y. pestis back to a mammalian host. While in the insect vector, proteins encoded by Hms genetic loci induce biofilm formation in the proventriculus, a valve connecting the midgut to the esophagus. Aggregation in the biofilm inhibits feeding and causes the flea to regurgitate blood. Transmission of Y. pestis occurs during the futile attempts of the flea to feed. Ingested blood is pumped into the esophagus, where it dislodges bacteria growing there and is regurgitated back into the host circulatory system (6). Pathogenesis due to Y. pestis infection of mammalian hosts is due to several factors including an ability of these bacteria to suppress and avoid normal immune system responses such as phagocytosis and antibody production. Flea bites allow for the bacteria to pass the skin barrier. Y. pestis expresses the yadBC gene, which is similar to adhesins in other Yersinia species. Y. pestis expresses a plasminogen activator that is an important virulence factor for pneumonic plague and that might degrade on blood clots in order to facilitate systematic invasion. Many of the bacteria's virulence factors are anti-phagocytic in nature. Two important anti-phagocytic antigens, named F1 (Fraction 1) and V or LcrV, are both important for virulence(5). These antigens are produced by the bacterium at normal human body temperature. Furthermore, Y. pestis survives and produces F1 and V antigens while it is residing within white blood cells such as monocytes, but not in neutrophils. Natural or induced immunity is achieved by the production of specific opsonic antibodies against F1 and V antigens; antibodies against F1 and V induce phagocytosis by neutrophils. In addition, the Type III secretion system (T3SS) allows Y. pestis to inject proteins into macrophages and other immune cells. These T3SS-injected proteins are called Yops (Yersinia Outer Proteins) and include Yop B/D, which form pores in the host cell membrane and have been linked to cytolysis. The injected Yop proteins limit phagocytosis and cell signaling pathways important in the innate immune system. Yersinia pestis proliferates inside lymph nodes where it is able to avoid destruction by cells of the immune system such as macrophages (3). A list is shown below illustrating the symptoms that occur with Y. pestis CO92 infection.
Incubation period of 2–6 days(bacteria is actively replicating) Lethargy Fever Headache and chills occur suddenly at the end of the incubation period Swelling of lymph nodes resulting in buboes, the classic sign of bubonic plague. The inguinal nodes (groin) are most frequently affected
The traditional first line treatment for Y. pestis has been streptomycin, chloramphenicol, tetracycline, and fluoroquinolones (4).
The attempts to find cures for the plague started the momentum toward development of the scientific method and the changes in thinking that led to the Renaissance. Early attempts at curing the plague included surrounding a victim with horrible smelling substances such as feces and urine. As the population dwindled and society crumbled, old rules were ignored. The Catholic church lost influence, creating the seeds that led to Protestantism. Colognes were also used more often during the Black Death period to cover up odors of dead flesh or unwashed clothing (4).
1. Aboudharam, G., Crubezy, E., Drancourt, M., Larrouy, G. 2001. Raoult, D. Molecular identification by “suicide PCR” of Yersinia pestis as the agent of Medieval Black Death. PNAS. 97(23) 12800-12820.
2. Arnold, P. 2009. How Does Yersinia Pestis Attack and Spread? Bright Hub: The Hub for Bright Minds. http://www.brighthub.com/science/genetics/articles/50016.aspx
3. Bliska J.B., Mejía E., Viboud G. 2009. Yersinia Controls Type III Effector Delivery into Host Cells by Modulating Rho Activity. PLoS ONE. 4(2): e4431.
4. Byrne, J. P. 2004. The black death. Westport: Greenwood Pub Group.
5. Collins, F. M. 1996. Pasteurella, Yersinia, and Francisella. Baron's Medical Microbiology. 4th edition.
6. Hinnebusch, B. J., R.D. Perry and T.G. Schwan. 1996. Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas. Science. 273(5237): 367–70.
7. Hixson, K. 2006. Biomarker candidate identification in Yersinia pestis using organism-wide semiquantitative proteomics. Journal of Proteome Research. 5(11): 3008–3017.
8. Inglesby, T., D. Dennis, D. Henderson, J Bartlett, M. Ascher, E. Eitzen, A. Fine, A. Friedlander, J. Hauer, J. Koerner, M. Layton, J. McDade, M. Osterholm, T. O'Toole, G. Parker, T. Perl, P. Russell, M. Schhoch-Spana, K. Tonat. 2000. Plague as a biological weapon: Medical and public health management. Journal of the American Medical Association. 283(17):2281-2290.
9. Meyer, K.F. (1957). The natural history of plague and psittacosis: The R. E. Dyer Lecture. Public Health Rep 72 (8): 705–19.
10. Parkhill, J., Wren, B.W., Thomson, N.R., Titball, R.W., Holden, M.T., Prentice, M.B., Sebaihia, M., James, K.D., Churcher, C., Mungall, K.L., Baker, S., Basham, D., Bentley, S.D., Brooks, K., Cerdeno-Tarraga, A.M., Chillingworth, T., Cronin, A., Davies, R.M., Davis, P., Dougan, G., Feltwell, T., Hamlin, N., Holroyd, S., Jagels, K., Karlyshev, A.V., Leather, S., Moule, S., Oyston, P.C., Quail, M., Rutherford, K., Simmonds, M., Skelton, J., Stevens, K., Whitehead, S., and Barrell, B.G. 2001. Genome sequence of Yersinia pestis, the causative agent of plague. Nature. 413:523-527
11. Perry R.D., J.D. Fetherston. 1997. Yersinia pestis: etiologic agent of plague. Clinical Microbiology. 10(1):35.