Yersinia pestis[
]
/ref> All three forms were responsible for a number of high-mortality throughout human history, including: the sixth century's Plague of Justinian; the Black Death, which accounted for the death of at least one-third of the population between 1347 and 1353; the Great Plague of London of 1665 which was ended in 1666 by the Great Fire of London; and the Third Pandemic, sometimes referred to as the Modern Plague, which began in the late nineteenth century in China and spread by rats on steamboats, claiming close to 10,000,000 lives.[ These plagues likely originated in China and were transmitted west via trade routes.][Zhang, Sarah, " An Ancient Case of the Plague Could Rewrite History", The Atlantic, December 6, 2018] This would push the date to much earlier and might be indicative of an origin in Europe rather than Eurasia.
Y. pestis was discovered in 1894 by Alexandre Yersin, a Switzerland/France physician and bacteriologist from the Pasteur Institute, during an epidemic of the plague in Hong Kong.
Every year, thousands of cases of the plague are still reported to the World Health Organization, although with proper treatment, the prognosis for victims is now much better. A five- to six-fold increase in cases occurred in Asia during the time of the Vietnam War, possibly due to the disruption of ecosystems and closer proximity between people and animals. The plague is now commonly found in sub-Saharan Africa and Madagascar, areas which now account for over 95% of reported cases. The plague also has a detrimental effect on nonhuman mammals.[CDC, "The Plague", Centers for Disease Control and Prevention, Oct. 2017 ] In the United States, mammals such as the black-tailed prairie dog and the endangered black-footed ferret are under threat.
General characteristics
Y. pestis is a nonmotile, stick-shaped, facultative anaerobic bacterium with bipolar staining (giving it a safety pin appearance) that produces an antiphagocytic slime layer.
Genome
The complete genome sequence is available for two of the three subspecies of Y. pestis: strain KIM (of biovar Y. p. medievalis),
A comprehensive and comparative proteomics analysis of Y. pestis strain KIM was performed in 2006.
Small noncoding RNA
Numerous bacterial small noncoding RNAs have been identified to play regulatory functions. Some can regulate the virulence genes. Some 63 novel putative sRNAs were identified through deep sequencing of the Y. pestis sRNA-ome. Among them was Yersinia-specific (also present in Y. pseudotuberculosis and Y. enterocolitica) Ysr141 ( Yersinia small RNA 141). Ysr141 sRNA was shown to regulate the synthesis of the type III secretion system (T3SS) effector protein YopJ.
Pathogenesis and immunity
In the urban and sylvatic (forest) cycles of Y. pestis, most of the spreading occurs between rodents and fleas. In the sylvatic cycle, the rodent is wild, but in the urban cycle, the rodent is primarily the brown rat. In addition, Y. pestis can spread from the urban environment and back. Transmission to humans is usually through the bite of infected fleas. If the disease has progressed to the pneumonic form, humans can spread the bacterium to others by coughing, vomiting and possibly sneezing.
In reservoir hosts
Several species of rodents serve as the main reservoir for Y. pestis in the environment. In the , the natural reservoir is believed to be principally the marmot. In the western United States, several species of are thought to maintain Y. pestis. However, the expected disease dynamics have not been found in any rodent. Several species of rodents are known to have a variable resistance, which could lead to an asymptomatic carrier status.
The 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 in a massive effect on prairie food webs.
In other regions of the world, the reservoir of the infection is not clearly identified, which complicates prevention and early-warning programs. One such example was seen in a 2003 outbreak in Algeria.
Vector
The transmission of Y. pestis by fleas is well characterized.
The hemin storage system plays an important role in the transmission of Y. pestis back to a mammalian host.
In humans and other susceptible hosts
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 a plasmin activator that is an important virulence factor for pneumonic plague and that might degrade on blood clots to facilitate systematic invasion.[ 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 , but not in . Natural or induced immunity is achieved by the production of specific opsonin antibody 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, called Yersinia outer proteins (Yops), include Yop B/D, which form pores in the host cell membrane and have been linked to cytolysis. The YopO, YopH N, YopM, YopT, YopJ, and YopE are injected into the cytoplasm of host cells by T3SS into the pore created in part by YopB and YopD.
Y. pestis cell growth inside , where it is able to avoid destruction by cells of the immune system such as . The ability of Y. pestis to inhibit phagocytosis allows it to grow in lymph nodes and cause lymphadenopathy. YopH is a protein tyrosine phosphatase that contributes to the ability of Y. pestis to evade immune system cells.
YopE functions as a GTPase-activating protein for members of the Rho family of GTPases such as RAC1. YopT is a cysteine protease that inhibits RHOA by removing the Prenylation, which is important for localizing the protein to the cell membrane. YopE and YopT has been proposed to function to limit YopB/D-induced cytolysis.
YopJ is an acetyltransferase that binds to a conserved Alpha helix of MAPK kinases.
Depending on which form of the plague with which the individual becomes infected, the plague develops a different illness; however, the plague overall affects the host cell’s ability to communicate with the immune system, hindering the body to bring phagocytic cells to the area of infection.
Y. pestis is a versatile killer. In addition to rodents and humans, it is known to have killed dogs, cats, camels, chickens, and pigs.
Immunity
A formaldehyde-inactivated vaccine once was available in the United States for adults at high risk of contracting the plague until removal from the market by the Food and Drug Administration. It was of limited effectiveness and could 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 such that vaccines composed of these antigens may not be fully protective.
Isolation and identification
In 1894, two bacteriologists, Alexandre Yersin of Switzerland and Kitasato Shibasaburō of Japan, independently isolated in Hong Kong the bacterium responsible for the Third Pandemic. Though both investigators reported their findings, a series of confusing and contradictory statements by Kitasato eventually led to the acceptance of Yersin as the primary discoverer of the organism. Yersin named it Pasteurella pestis in honor of the Pasteur Institute, where he worked. In 1967, it was moved to a new genus and renamed Yersinia pestis in his honor. Yersin also noted that rats were affected by plague not only during plague epidemics, but also often preceding such epidemics in humans and that plague was regarded by many locals as a disease of rats; villagers in China and India asserted that, when large numbers of rats were found dead, plague outbreaks soon followed.
In 1898, French scientist Paul-Louis Simond (who had also come to China to battle the Third Pandemic) established the rat-flea vector that drives the disease. He had noted that persons who became ill did not have to be in close contact with each other to acquire the disease. In Yunnan, China, inhabitants would flee from their homes as soon as they saw dead rats, and on the island of Formosa (Taiwan), residents considered the handling of dead rats heightened the risks of developing plague. These observations led him to suspect that the flea might be an intermediary factor in the transmission of plague, since people acquired plague only if they were in contact with recently dead rats, that had died less than 24 hours before. In a now classic experiment, Simond demonstrated how a healthy rat died of plague, after infected fleas had jumped to it, from a rat which had recently died of the plague.[Chase, M. (2004). The Barbary Plague: The Black Death in Victorian San Francisco. Random House Trade Paperbacks.]
Ancient DNA evidence
In 2018, the emergence and spread of the pathogen during the Neolithic Decline (as far back as 6,000 years ago) was published.[Rascovan, Nicolas, et al, Emergence and Spread of Basal Lineages of Yersinia pestis during the Neolithic Decline, Cell, December 6, 2018, ] A site in Sweden was the source of the DNA evidence and trade networks were proposed as the likely avenue of spread rather than migrations of populations.
DNA evidence published in 2015 indicates Y. pestis infected humans 5,000 years ago in Bronze Age
Eurasia,[ This article contains quotations from this source, which is available under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.] but genetic changes that made it highly virulent did not occur until about 4,000 years ago.[ This article contains quotations from this source, which is available under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.] The highly virulent version capable of transmission by fleas through rodents, humans, and other mammals was found in two individuals associated with the Srubnaya culture from the Samara Oblast in Russia from around 3,800 years ago and an Iron Age individual from Kapan, Armenia from around 2,900 years ago.
Three main strains are recognised: Antiqua, which caused a plague pandemic in the sixth century; Medievalis, which caused the Black Death and subsequent epidemics during the second pandemic wave; and Orientalis, which is responsible for current plague outbreaks.
Plague causes a blockage in the proventriculus of the flea by forming a biofilm.
Recent events
In 2008, the plague was commonly found in sub-Saharan Africa and Madagascar, areas which accounted for over 95% of the reported cases.
In September 2009, the death of Malcolm Casadaban, a molecular genetics professor at the University of Chicago, was linked to his work on a weakened laboratory strain of Y. pestis.
In 2012, researchers in Germany collected samples of Y. pestis from gravesites with a view to reconstructing the DNA of the bacterium.
On June 8, 2015 in Larimer County, CO, a fatality was confirmed by the CDC as listed on the RSOE EDIS – Emergency and Disaster Information Service.
On September 8, 2016, the Y. pestis bacterium was identified from DNA in teeth found at a Crossrail building site in London. The human remains were found to be victims of the Great Plague of London, which lasted from 1665 to 1666.
On January 15, 2018, researchers at the University of Oslo and the University of Ferrara suggested that humans and their parasites were the biggest carriers of the plague.
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