Yersinia pestis

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Yersinia pestis
A scanning electron micrograph depicting a mass of Yersinia pestis bacteria
Scientific classification
Kingdom: Eubacteria Phylum: Proteobacteria Class: Gammaproteobacteria Order: Enterobacteriales Family: Enterobacteriaceae Genus: Yersinia Species: Y. pestis
Binomial name
Yersinia pestis (Lehmann & Neumann, 1896) van Loghem 1944

Yersinia pestis (Pasteurella pestis) is a Gram-negative bacillus bacterium belonging to the family Enterobacteriaceae. It is a facultative anaerobic bipolar-staining cell (giving it a safety pin appearance).^[1]

Human Y. pestis infection have three main forms, the well-known is bubonic, pneumonic, and septicemic plague.^[2] All three forms have been responsible for high mortality rates in epidemics throughout human history, including the Black Death that accounted for the death of approximately one-third of the European population in 1347 to 1353. The genus Yersinia is Gram-negative, bipolar staining coccobacilli, and, similarly to other Enterobacteriaceae. The closest relative is the gastrointestinal pathogen Yersinia pseudotuberculosis, and more distantly Yersinia enterocolitica.

Recently Yersinia pestis has gained attention as a possible biological warfare agent and the CDC has classified Y. pestis as category A pathogen requiring preparation for a possible terrorist attack.

Contents 1 Discovery 2 General characteristics 2.1 Genome 3 Pathogenics and immunity 3.1 In reservoir host 3.2 In vector 3.3 In humans and other susceptible hosts 3.4 Immunity 4 Clinical aspects 4.1 Symptoms and disease progression 4.2 Clinical determination 4.3 Treatment 5 Historical impact 6 External links 7 References

[edit] Discovery

Y. pestis was discovered in 1894 by a Swiss/French physician and bacteriologist from the Pasteur Institute, Alexandre Yersin, during an epidemic of plague in Hong Kong.^[3] Yersin was a member of the Pasteur school of thought. Shibasaburo Kitasato, a German-trained Japanese bacteriologist who practiced Koch's methodology was also engaged at the time in finding the causative agent of plague.^[4] However, it was Yersin who actually linked plague with Yersinia pestis. Originally named Pasteurella pestis, the organism was renamed in 1967.

Three biovars of Y. pestis are known, each thought to correspond to one of the historical pandemics of bubonic plague.^[5] Biovar Antiqua is thought to correspond to the Plague of Justinian; it is not known whether this biovar also corresponds to earlier, smaller epidemics of bubonic plague, or whether these were even truly bubonic plague.^[6] Biovar Medievalis is thought to correspond to the Black Death. Biovar Orientalis is thought to correspond to the Third Pandemic and the majority of modern outbreaks of plague. Y. pestis was carried on rats' fleas.

[edit] General characteristics

Y. pestis is similar to other Yersinia members test negative for the urease, lactose-fermentation, and indole tests.^[7]

[edit] Genome

The complete genomic sequence is available for two of the three sub-species of Y. pestis: strain KIM (of biovar Medievalis),^[8] and strain CO92 (of biovar Orientalis, obtained from a clinical isolate in the United States)^[9]; as of 2006, the genomic sequence of a strain of biovar Antiqua has been recently completed.^[10] Similar to the other pathogenic strains, there are signs of the loss of function as adaptive lost. The chromosome of strain KIM is 4,600,755 base pairs long; the chromosome of strain CO92 is 4,653,728 base pairs long. Like its cousins Y. pseudotuberculosis and Y. enterocolitica, Y. pestis is host to the plasmid pCD1. In addition, it also hosts two other plasmids, pPCP1 and pMT1 which are not carried by the other Yersinia species. Together, these plasmids, and a pathogenicity island called HPI, encode several proteins which cause the pathogenesis for which Y. pestis is famous. Among other things, these virulence factors are required for bacterial adhesion and injection of proteins into the host cell, invasion of bacteria into the host cell, and acquisition and binding of iron harvested from red blood cells. Y. pestis is thought to be descendant from Y. pseudotuberculosis, differing only in the presence of specific virulence plasmids.

A recent comprehensive and comparative proteomics analysis of Y. pestis: strain KIM was recently performed,^[11] this analysis focused on the transition to a growth condition mimicking growth in host cells.

[edit] Pathogenics and immunity

[edit] In reservoir host

The reservoir commonly associated with Y. pestis are several species of rodents. In the steppes the reservoir species are principally believed to be marmots. While in the United States, several species of rodents are thought maintain Y. pestis. However, the case is not very clear because the expected disease dynamics have not been found in any rodent species. It is known that some individuals in a rodent population will have a different resistance, which could lead to a carrier status^[12]. There is some evidence that fleas from other mammals have a role in human plague outbreaks^[13].

This lack of knowledge of the dynamics of plague in mammal species is also true among susceptible rodents such as the black-tailed prairie dog (Cynomys ludovicianus), in which plague can cause colony collapse resulting a massive effect on prairie food webs^[14]. However, the transmission dynamics within prairie dogs does not follow the dynamics of blocked fleas; this study's authors believe that carcasses, unblocked fleas, or another vector might be important^[15].

In other regions of the world the reservoir of the infection is not clearly identified, which complicates prevention and early warning programs. One such is example was the 2003 outbreak in Algeria^[16].

[edit] In vector

The transmission of Y. pestis by fleas is well characterized^[17]. Initial acquisition of Y. pestis by the vector occurs during 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).

Although Ymt is highly toxic to rodents and was once thought to be produced to insure reinfection of new hosts, it has been demonstrated that murine toxin is important for the survival of Y. pestis in fleas^[18].

The Hms system plays an important role in the transmission of Y. pestis back to a mammalian host^[19]. The proteins encoded by Hms genetic loci aggregate in the esophagus and proventriculus of the flea, which is a structure that ruptures blood cells. Aggregation of Hms proteins inhibits feeding and causes the flea to feel hungry. 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.

[edit] In humans and other susceptible hosts

Pathogenesis of Y. pestis in mammalian host is due to several factors, which predominately focus on the initial immune response. Flea bite allow for the bacteria through the skin, Y. pestis also expresses the yadBC gene, which is similar to Invasin in other Yersinia species, allowing for adherence and invasion of epithelium.^[20] There are reports that isolates from the pneumatic plague patients have a plasminogen activator , which can remove clots in order for systematic invasion. ^[21] The majority of the Y. pestis 's virulence factors are anti-phagocytic in nature. Two important anti-phagocytic antigens, named F1 (Fraction 1) and V, both important for virulence.^[1] These antigens are produced by the bacterium at normal human body Temperature of 37 C. Furthermore, Y. pestis survives and produces F1 and V antigens within blood cells such as monocytes, but not in polymorphonuclear 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.^[22]

Additionally the Type III secretion system injects into macrophage and other immune cells six different effectors collective call YOP( Yersinia Outercoat Proteins) YopO, YopH, YopM, YopT, YopJ, and YopE. These proteins are injected via a long syringe into a pore created in part by YopB and YopD. ^[23] The next of the effects of these proteins to the limit phagocytosis by targeting [actin] and other cell singling pathway important in the innate immune system

[edit] Immunity

A formalin-inactivated vaccine once was available for adults at high risk of contracting the plague until removal from the market by the FDA. It was of limited effectiveness and may cause severe inflammation. Experiments with genetic engineering of a vaccine based on F1 and V antigens are underway and show promise; however, bacteria lacking antigen F1 are still virulent, and the V antigens are sufficiently variable, that vaccines composed of these antigens may not be fully protective^[24].

[edit] Clinical aspects

[edit] Symptoms and disease progression

• Bubonic plague
  • Incubation period of 2-6 days, when the bacteria is actively replicating in lymph nodes
  • Universally a general lack of energy
  • Fever
  • Headache and chills occur suddenly at the end of the incubation period. From this point the infection is resolved or lethal.
  • Swelling of lymph nodes resulting of buboes, this is the classic sign of bubonic plague

• Septicemic plague
  • Hypotension
  • Hepatosplenomegaly
  • Delirium
  • Seizures in children
  • Shock
  • Universally a general lack of energy
  • Fever
  • Symptoms of Bubonic or Pneumonic Plague, not always present

• Pneumonic plague
  • Fever
  • Chills
  • Cough
  • Chest pain
  • Dyspnea
  • Hemoptysis
  • Lethargy
  • Hypotension
  • Shock
  • Symptoms of bubonic or septicemic plague, not always present

From "Harrison's Principles of Internal Medicine 16th Edition"

If this occurs with the classic buboes, this is considered primary, while in secondary occurs after symptoms of bubonic or pneumonic infection. With the bacteria located in the blood, several organs can be affected including the spleen, and brain. With the delocalized infection, an immunologic cascade occurs, this can be seen by the occurrence of DIC, which in turn results in bleeding and narcotized skin and tissue. These widespread infections increase mortality to 22%.

Finally, Pneumonic plague can be from direct aerosol infection in which it is considered primary. While Bubonic, and to a lesser degree, Septicemic plague can gain pneumatic characteristic. As with the other forms of plague after the incubation period of a few hours to days there is sudden onset coughing, elevated temperature, and lack of energy. From this point the infection increases in severity in pneumonia. Due to the high replication rates, death with treated plague is roughly 50%, and almost universally fatal without treatment.^[25]

The initial symptoms of plague is very similar to other bacterial diseases, as well as some viral. image (http://www.cdc.gov/ncidod/dvbid/plague/p1.htm) with the exception of the buboes. make diagnosis difficult^[26].

This is the ICD-9 codes for the diseases caused by Y. pestis

• 020.0 Bubonic plague
• 020.2 Septicemic plague
• 020.5 Unspecified pneumonic plague
• 020.3 Primary pneumonic plague
• 020.4 Secondary pneumonic plague

[edit] Clinical determination

Grams stains can confirm the presence of gram negative rods, and in some cases the identification of the double curved shape. More definitive test is a Anti-F1 serology test, which can differentiate between different species of Yersinia.

[edit] Treatment

The traditional first line treatment for Y. pestis has been streptomycin,^[27][28] chloramphenicol, tetracycline,^[29] and fluoroquinolones. There is also good evidence to support the use of doxycycline or gentamicin.^[30]

It should be noted that strains resistant to one or two agents specified above have been isolated: treatment should be guided by antibiotic sensitivities where available. Antibiotic treatment alone is insufficient for some patients, who may also require circulatory, ventilator, or renal support.

In an emergency department setting, Harrison's principles of internal medicine outlines the following treatment course^[31]. Antibiotics within the first 24 hours is very beneficial, with intravenous being preferred in pulmonary or advance cases. streptomycin or gentamicin as the first-line drugs, with chloramphenicol for critical ill patients, or rarely for suspected neuro-involvement.

[edit] Historical impact

The role of Y. pestis in the Black Death is debated among historians; some have suggested that the Black Death spread far too rapidly to be caused by Y. pestis. DNA from Y. pestis is alleged to have been found in the teeth of an individual who supposedly died from the Black Death, however, and medieval corpses who died from other causes did test positive for Y. pestis.^[32][33] This suggests that Y. pestis was, at the very least, a contributing factor in some (though possibly not all) of the European plagues. It is possible that the selective pressures induced by the plague might have changed how the pathogen manifests in humans, selecting against the individuals or populations which were the most susceptible.

[edit] External links

• Yersinia pestis. Virtual Museum of Bacteria.
• Genome information is available from the NIAID Enteropathogen Resource Integration Center (ERIC)
• A list of variant strains and information on synonyms (and much more) is available through the NCBI taxonomy browser.

• CDC's Home page for Plague [1]

[edit] References