Yersinia pestis

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Yersinia pestis
Yersinia pestis.jpg
A scanning electron micrograph depicting a mass of Yersinia pestis bacteria in the foregut of an infected flea
Scientific classification
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Y. pestis
Synonyms

Bacillus

  • Bacille de la peste
    Yersin, 1894
  • Bacterium pestis
    Lehmann & Neumann, 1896
  • Pasteurella pestis
    (Lehmann & Neumann, 1896) Holland, 1920

Yersinia pestis [1] (formerly Pasteurella pestis) is a Gram-negative, nonmotile, rod-shaped, coccobacillus bacterium, with no spores. It is a facultative anaerobic organism that can infect humans via the Oriental rat flea. [2] It causes the disease plague, which takes three main forms: pneumonic, septicemic, and bubonic plagues. [2] [3] [4] All three forms were responsible for a number of high-mortality epidemics 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 European 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 19th century in China and spread by rats on steamboats, claiming close to 10,000,000 lives. [5] [6] [7] [8] These plagues likely originated in China and were transmitted west via trade routes. [8] [9] Recent research in 2018 indicated that the pathogen may have been the cause of what was described as the Neolithic Decline, in which European populations declined significantly. [10] This would push the date to much earlier and might be indicative of an origin in Europe rather than Eurasia.

<i>Pasteurella</i> genus of bacteria

Pasteurella is a genus of Gram-negative, facultatively anaerobic bacteria. Pasteurella species are nonmotile and pleomorphic, and often exhibit bipolar staining. Most species are catalase- and oxidase-positive. The genus is named after the French chemist and microbiologist, Louis Pasteur, who first identified the bacteria now known as Pasteurella multocida as the agent of chicken cholera.

Gram-negative bacteria group of bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation

Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the gram-staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane.

Non-motile bacteria

Non-motile bacteria are those bacterial species that lack the ability and structures that would allow them to propel themselves, under their own power, through their environment. When non-motile bacteria are cultured in a stab tube, they only grow along the stab line. If the bacteria are mobile, the line will appear diffuse and extend into the medium. The cell structures that provide the ability for locomotion are the cilia and flagella. Coliform and Streptococci are examples of non-motile bacteria as are Klebsiella pneumoniae, and Yersinia pestis. Motility is one characteristic used in the identification of bacteria and evidence of possessing structures: peritrichous flagella, polar flagella and/or a combination of both.

Contents

Y. pestis was discovered in 1894 by Alexandre Yersin, a Swiss/French physician and bacteriologist from the Pasteur Institute, during an epidemic of the plague in Hong Kong. [11] Yersin was a member of the Pasteur school of thought. Kitasato Shibasaburō, a German-trained Japanese bacteriologist who practised Koch's methodology, was also engaged at the time in finding the causative agent of the plague. [12] However, Yersin actually linked plague with Y. pestis. Named Pasteurella pestis in the past, the organism was renamed Yersinia pestis in 1944.

Alexandre Yersin Swiss and French physician and bacteriologist

Alexandre Emile Jean Yersin was a Swiss and naturalized French physician and bacteriologist. He is remembered as the co-discoverer of the bacillus responsible for the bubonic plague or pest, which was later named in his honour. Another bacteriologist, Kitasato Shibasaburō is often credited with independently identifying the bacterium a few days earlier but may have identified a different bacterium and not the pathogen causing plague. Yersin also demonstrated for the first time that the same bacillus was present in the rodent as well as in the human disease, thus underlining the possible means of transmission.

Switzerland Federal republic in Central Europe

Switzerland, officially the Swiss Confederation, is a sovereign state situated in the confluence of western, central, and southern Europe. It is a federal republic composed of 26 cantons, with federal authorities seated in Bern. Switzerland is a landlocked country bordered by Italy to the south, France to the west, Germany to the north, and Austria and Liechtenstein to the east. It is geographically divided between the Alps, the Swiss Plateau and the Jura, spanning a total area of 41,285 km2 (15,940 sq mi), and land area of 39,997 km2 (15,443 sq mi). While the Alps occupy the greater part of the territory, the Swiss population of approximately 8.5 million is concentrated mostly on the plateau, where the largest cities are located, among them the two global cities and economic centres of Zürich and Geneva.

France Republic in Europe with several non-European regions

France, officially the French Republic, is a country whose territory consists of metropolitan France in Western Europe and several overseas regions and territories. The metropolitan area of France extends from the Mediterranean Sea to the English Channel and the North Sea, and from the Rhine to the Atlantic Ocean. It is bordered by Belgium, Luxembourg and (Germany) to the northeast, Switzerland and Italy to the east, and Andorra and Spain to the south. The overseas territories include French Guiana in South America and several islands in the Atlantic, Pacific and Indian oceans. The country's 18 integral regions span a combined area of 643,801 square kilometres (248,573 sq mi) and a total population of 67.02 million. France is a unitary semi-presidential republic with its capital in Paris, the country's largest city and main cultural and commercial centre. Other major urban areas include Lyon, Marseille, Toulouse, Bordeaux, Lille and Nice.

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. [13] In the United States, mammals such as the black-tailed prairie dog and the endangered black-footed ferret are under threat.

World Health Organization Specialized agency of the United Nations

The World Health Organization (WHO) is a specialized agency of the United Nations that is concerned with international public health. It was established on 7 April 1948, and is headquartered in Geneva, Switzerland. The WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations.

Prognosis is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen or remain stable over time; expectations of quality of life, such as the ability to carry out daily activities; the potential for complications and associated health issues; and the likelihood of survival. A prognosis is made on the basis of the normal course of the diagnosed disease, the individual's physical and mental condition, the available treatments, and additional factors. A complete prognosis includes the expected duration, function, and description of the course of the disease, such as progressive decline, intermittent crisis, or sudden, unpredictable crisis.

Vietnam War 1955–1975 conflict in Vietnam

The Vietnam War, also known as the Second Indochina War, and in Vietnam as the Resistance War Against America or simply the American War, was a conflict in Vietnam, Laos, and Cambodia from 1 November 1955 to the fall of Saigon on 30 April 1975. It was the second of the Indochina Wars and was officially fought between North Vietnam and South Vietnam. North Vietnam was supported by the Soviet Union, China, and other communist allies; South Vietnam was supported by the United States, South Korea, the Philippines, Australia, Thailand and other anti-communist allies. The war, considered a Cold War-era proxy war by some, lasted 19 years, with direct U.S. involvement ending in 1973, and included the Laotian Civil War and the Cambodian Civil War, which ended with all three countries becoming communist in 1975.

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. [14] Similar to other Yersinia species, it tests negative for urease, lactose fermentation, and indole. [15] Its closest relative is the gastrointestinal pathogen Yersinia pseudotuberculosis , and more distantly Yersinia enterocolitica .

Safety pin pointed fastener with a locking mechanism, often used to secure clothing and cloth diapers

The safety pin is a variation of the regular pin which includes a simple spring mechanism and a clasp. The clasp serves two purposes: to form a closed loop thereby properly fastening the pin to whatever it is applied to, and to cover the end of the pin to protect the user from the sharp point.

<i>Yersinia</i> genus of bacteria

Yersinia is a genus of bacteria in the family Yersiniaceae. Yersinia species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of Yersinia are pathogenic in humans; in particular, Y. pestis is the causative agent of the plague. Rodents are the natural reservoirs of Yersinia; less frequently, other mammals serve as the host. Infection may occur either through blood or in an alimentary fashion, occasionally via consumption of food products contaminated with infected urine or feces.

The indole test is a biochemical test performed on bacterial species to determine the ability of the organism to convert tryptophan into indole. This division is performed by a chain of a number of different intracellular enzymes, a system generally referred to as "tryptophanase."

Genome

The complete genomic sequence is available for two of the three subspecies of Y. pestis: strain KIM (of biovar Y. p. medievalis), [16] and strain CO92 (of biovar Y. p. orientalis, obtained from a clinical isolate in the United States). [17] As of 2006, the genomic sequence of a strain of biovar Antiqua has been recently completed. [18] Similar to the other pathogenic strains, signs exist of loss of function mutations. 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 Y. pseudotuberculosis and Y. enterocolitica, Y. pestis is host to the plasmid pCD1. It also hosts two other plasmids, pPCP1 (also called pPla or pPst) and pMT1 (also called pFra) that are not carried by the other Yersinia species. pFra codes for a phospholipase D that is important for the ability of Y. pestis to be transmitted by fleas. [19] pPla codes for a protease, Pla, that activates plasmin in human hosts and is a very important virulence factor for pneumonic plague. [20] Together, these plasmids, and a pathogenicity island called HPI, encode several proteins that 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 in the host cell (via a type-III secretion system), and acquisition and binding of iron harvested from red blood cells (by siderophores). Y. pestis is thought to be descended from Y. pseudotuberculosis , differing only in the presence of specific virulence plasmids.

Genome entirety of an organisms hereditary information; genome of organism (encoded by the genomic DNA) is the (biological) information of heredity which is passed from one generation of organism to the next; is transcribed to produce various RNAs

In the fields of molecular biology and genetics, a genome is the genetic material of an organism. It consists of DNA. The genome includes both the genes and the noncoding DNA, as well as mitochondrial DNA and chloroplast DNA. The study of the genome is called genomics.

Chromosome DNA molecule containing genetic material of a cell

A chromosome is a deoxyribonucleic acid (DNA) molecule with part or all of the genetic material (genome) of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle.

Plasmid small DNA molecule within a cell that is physically separated from a chromosomal DNA and can replicate independently

A plasmid is a small DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; however, plasmids are sometimes present in archaea and eukaryotic organisms. In nature, plasmids often carry genes that benefit the survival of the organism, such as by providing antibiotic resistance. While the chromosomes are big and contain all the essential genetic information for living under normal conditions, plasmids usually are very small and contain only additional genes that may be useful in certain situations or conditions. Artificial plasmids are widely used as vectors in molecular cloning, serving to drive the replication of recombinant DNA sequences within host organisms. In the laboratory, plasmids may be introduced into a cell via transformation.

A comprehensive and comparative proteomics analysis of Y. pestis strain KIM was performed in 2006. [21] The analysis focused on the transition to a growth condition mimicking growth in host cells.

Proteomics study of proteins

Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions. The term proteomics was coined in 1997, in analogy to genomics, the study of the genome. The word proteome is a portmanteau of protein and genome, and was coined by Marc Wilkins in 1994 while he was a Ph.D. student at Macquarie University. Macquarie University also founded the first dedicated proteomics laboratory in 1995.

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. [22] The Yop-Ysc T3SS is a critical component of virulence for Yersinia species. [23] Many novel sRNAs were identified from Y. pestis grown in vitro and in the infected lungs of mice suggesting they play role in bacterial physiology or pathogenesis. Among them sR035 predicted to pair with SD region and transcription initiation site of a thermo-sensitive regulator ymoA, and sR084 predicted to pair with fur, ferric uptake regulator. [24]

Pathogenesis and immunity

Oriental rat flea (Xenopsylla cheopis) infected with the Y. pestis bacterium, which appears as a dark mass in the gut: The foregut (proventriculus) of this flea is blocked by a Y. pestis biofilm; when the flea attempts to feed on an uninfected host, Y. pestis is regurgitated into the wound, causing infection. Flea infected with yersinia pestis.jpg
Oriental rat flea (Xenopsylla cheopis) infected with the Y. pestis bacterium, which appears as a dark mass in the gut: The foregut (proventriculus) of this flea is blocked by a Y. pestis biofilm; when the flea attempts to feed on an uninfected host, Y. pestis is regurgitated into the wound, causing infection.

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 steppes, the natural reservoir is believed to be principally the marmot. In the western United States, several species of rodents 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. [25] Evidence indicates fleas from other mammals have a role in human plague outbreaks. [26]

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. [27] However, the transmission dynamics within prairie dogs do not follow the dynamics of blocked fleas; carcasses, unblocked fleas, or another vector could possibly be important, instead. [28]

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. [29] Domestic house cats are susceptible to plague. Their symptoms are similar to those experienced by humans. Cats infected with plague can infect people through bites, scratches, coughs, or sneezes. [30]

Vector

The transmission of Y. pestis by fleas is well characterized. [31] 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 system and Yersinia murine toxin (Ymt). Although Ymt is highly toxic to rodents and was once thought to be produced to ensure reinfection of new hosts, it is important for the survival of Y. pestis in fleas. [19]

The hemin storage system plays an important role in the transmission of Y. pestis back to a mammalian host. [32] While in the insect vector, proteins encoded by hemin storage system genetic loci induce biofilm formation in the proventriculus, a valve connecting the midgut to the esophagus. [33] Aggregation in the biofilm inhibits feeding, as a mass of clotted blood and bacteria forms (referred to as "Bacot's block" after entomologist A.W. Bacot, the first to describe this phenomenon). [34] 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 lodged in the proventriculus which is regurgitated back into the host circulatory system. [35]

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. [20] Many of the bacteria's virulence factors are antiphagocytic in nature. Two important antiphagocytic antigens, named F1 (fraction 1) and V or LcrV, are both important for virulence. [14] 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. [36]

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, 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. [37] The injected Yops limit phagocytosis and cell signaling pathways important in the innate immune system, as discussed below. In addition, some Y. pestis strains are capable of interfering with immune signaling (e.g., by preventing the release of some cytokines).

Y. pestis proliferates inside lymph nodes, where it is able to avoid destruction by cells of the immune system such as macrophages. 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. [38] In macrophages, YopH has been shown to dephosphorylate p130Cas, Fyb (Fyn binding protein) SKAP-HOM and Pyk, a tyrosine kinase homologous to FAK. YopH also binds the p85 subunit of phosphoinositide 3-kinase, the Gab1, the Gab2 adapter proteins, and the Vav guanine nucleotide exchange factor.

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 isoprenyl group, 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. [39] This might limit the function of YopB/D to create the pores used for Yop insertion into host cells and prevent YopB/D-induced rupture of host cells and release of cell contents that would attract and stimulate immune system responses.

YopJ is an acetyltransferase that binds to a conserved α-helix of MAPK kinases. [40] YopJ acetylates MAPK kinases at serines and threonines that are normally phosphorylated during activation of the MAP kinase cascade. [41] [42] YopJ is activated in eukaryotic cells by interaction with target cell Phytic acid (IP6). [43] This disruption of host cell protein kinase activity causes apoptosis of macrophages, and this is proposed to be important for the establishment of infection and for evasion of the host immune response. YopO is a protein kinase also known as Yersinia protein kinase A (YpkA). YopO is a potent inducer of human macrophage apoptosis. [44]

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. [45]

Immunity

A formalin-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. [46] The United States Army Medical Research Institute of Infectious Diseases has found that an experimental F1/V antigen-based vaccine protects crab-eating macaques, but fails to protect African green monkey species. [47] A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine. [48]

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.[ citation needed ]

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. [49] The outbreak spread to Chinatown, San Francisco from 1900 to 1904 and then to Oakland and the East Bay from 1907 to 1909. [50] It has been present in the rodents of western North America ever since, as fear of the consequences of the outbreak on trade caused authorities to hide the dead of the Chinatown residents long enough for the disease to be passed to widespread species of native rodents in outlying areas. [51]

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. [52] 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, [53] but genetic changes that made it highly virulent did not occur until about 4,000 years ago. [54] 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 region in Russia from around 3,800 years ago and an Iron Age individual from Kapan, Armenia from around 2,900 years ago. [54] [53] This indicates that at least two lineages of Y. pestis were circulating during the Bronze Age in Eurasia. [54] The Y. pestis bacterium has a relatively large number of nonfunctioning genes and three "ungainly" plasmids, suggesting an origin less than 20,000 years ago. [45]

Three main strains are recognised: Y. p. antiqua, which caused a plague pandemic in the sixth century; Y. p. medievalis, which caused the Black Death and subsequent epidemics during the second pandemic wave; and Y. p. orientalis, which is responsible for current plague outbreaks. [55]

Plague causes a blockage in the proventriculus of the flea by forming a biofilm. [56] The biofilm formation is induced by the ingestion of blood. The presence of a biofilm seems likely to be required for stable infection of the flea. [57] It has been suggested that a bacteriophage  – Ypφ – may have been responsible for increasing the virulence of this organism. [58]

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. [13]

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. [59] Hemochromatosis was hypothesised to be a predisposing factor in Casadaban's death from this attenuated strain used for research. [60]

In 2010, researchers in Germany definitely established, using PCR evidence from samples obtained from Black Death victims, that Y. pestis was the cause of the medieval Black Death. [61]

In 2011, the first genome of Y. pestis isolated from Black Death victims was published, and concluded that this medieval strain was ancestral to most modern forms of Y. pestis. [62]

In 2015, Cell published results from a study of ancient graves. Plasmids of Y. pestis were detected in archaeological samples of the teeth of seven Bronze Age individuals, in the Afanasievo culture in Siberia, the Corded Ware culture in Estonia, the Sintashta culture in Russia, the Unetice culture in Poland, and the Andronovo culture in Siberia. [63]

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. [3]

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. [64]

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. [65] [66]

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Braun's lipoprotein, found in some gram-negative cell walls, is one of the most abundant membrane proteins; its molecular weight is about 7.2 kDa. It is bound at its C-terminal end by a covalent bond to the peptidoglycan layer and is embedded in the outer membrane by its hydrophobic head. BLP tightly links the two layers and provides structural integrity to the outer membrane.

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Virulence factors are molecules produced by bacteria, viruses, fungi, and protozoa that add to their effectiveness and enable them to achieve the following:

LcrV

In molecular biology, LcrV is a protein found in Yersinia pestis and several other bacterial species. It forms part of the Yersinia pestis virulence protein factors that also includes all Yops, or Yersinia outer protein, but the name has been kept out of convention. LcrV's main function is not actually known, but it is essential for the production of other Yops.

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Plague vaccine chemical compound

Plague vaccine is a vaccine used against Yersinia pestis. Killed bacteria have been used since 1890 but are less effective against pneumonic plague so that recently live vaccines of an attenuated type and recombination protein vaccines have been developed to prevent the disease.

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Yersiniabactin chemical compound

Yersiniabactin (Ybt) is a siderophore found in the pathogenic bacteria Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica, as well as several strains of enterobacteria including enteropathogenic Escherichia coli and Salmonella enterica. Siderophores, compounds of low molecular mass with high affinities for ferric iron, are important virulence factors in pathogenic bacteria. Iron—an essential element for life used for such cellular processes as respiration and DNA replication—is extensively chelated by host proteins like lactoferrin and ferritin; thus, the pathogen produces molecules with an even higher affinity for Fe3+ than these proteins in order to acquire sufficient iron for growth. As a part of such an iron-uptake system, yersiniabactin plays an important role in pathogenicity of Y. pestis, Y. pseudotuberculosis, and Y. entercolitica.

YopH, N-terminal

In molecular biology, YopH, N-terminal refers to an evolutionary conserved protein domain. This entry represents the N-terminal domain of YopH protein tyrosine phosphatase (PTP).

YopR bacterial protein domain

In molecular biology, YopR is a protein domain commonly found in gram negative bacteria, in particular Yersinia and is a core domain. Proteins in this entry are type III secretion system effectors. They are named differently in different species and in Yersinia has been designated YopR which is encoded by the YscH gene. This Yop protein is unusual in that it is released to the extracellular environment rather than injected directly into the target cell as are most Yop proteins. A hallmark of Yersinia type III machines is the presence of needles extending from the bacterial surface. Needles perform two functions, firstly, as a channel to export effectors into the immune cells and secondly as a sensor.

TyeA protein domain


In molecular biology, the protein domain TyeA is short for Translocation of Yops into eukaryotic cells A. It controls the release of Yersinia outer proteins (Yops) which help Yersinia evade the immune system. More specifically, it interacts with the bacterial protein YopN via hydrophobic residues located on the helices.

YadA bacterial adhesin protein domain

In molecular biology, YadA is a protein domain which is short for Yersinia adhesin A. These proteins have strong sequence and structural homology, particularly at their C-terminal end. The function is to promote their pathogenicity and virulence in host cells, though cell adhesion. YadA is found in three pathogenic species of Yersinia, Y. pestis,Y. pseudotuberculosis, and Y. enterocolitica. The YadA domain is encoded for by a virulence plasmid in Yersinia, which encodes a type-III secretion (T3S) system consisting of the Ysc injectisome and the Yop effectors.

Yersinia phage L-413C is a virus of the family Myoviridae, genus P2likevirus.

Sylvatic plague is an infectious bacterial disease caused by the bacterium Yersinia pestis that primarily affects rodents such as prairie dogs. It is the same bacterium that causes bubonic and pneumonic plague in humans. Sylvatic, or sylvan, means 'occurring in wildlife,' and refers specifically to the form of plague in rural wildlife. Urban plague refers to the form in urban wildlife.

Bacterial effector protein

Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague, the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a novel membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.

References

  1. Sutyak, Katya (10 November 2015). "Student presentation on Yersinia pestis". University of Connecticut. Archived from the original on 12 September 2013.
  2. 1 2 Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 484–488. ISBN   978-0-8385-8529-0.
  3. 1 2 hunnomad@gmail.com, Zsolt Boszormenyi-. "RSOE EDIS - - Event reports (Earthquakes, events, tropical storms, tsunamies and others)". RSOE EDIS. Retrieved 11 December 2018.
  4. CDC https://www.cdc.gov/plague/
  5. Alchon, Suzanne Austin (2003). A pest in the land: new world epidemics in a global perspective. University of New Mexico Press. p. 21. ISBN   978-0-8263-2871-7.
  6. Harbeck, Michaela; Seifert, Lisa; Hänsch, Stephanie; Wagner, David M.; Birdsell, Dawn; Parise, Katy L.; Wiechmann, Ingrid; Grupe, Gisela; Thomas, Astrid; Keim, Paul; Zöller, Lothar; Bramanti, Barbara; Riehm, Julia M.; Scholz, Holger C. (2013). "Yersinia pestis DNA from Skeletal Remains from the 6th Century AD Reveals Insights into Justinianic Plague | Science. New SeriesPLoS Pathogens". PLoS Pathogens. 9 (#5): e1003349. doi:10.1371/journal.ppat.1003349. PMC   3642051 . PMID   23658525. Lay summary ScienceDaily (May 10, 2013).
  7. Carter, Adam (January 27, 2014). "Black Death mysteries unlocked by McMaster scientists". CBC News.
  8. 1 2 Nicholas Wade (October 31, 2010). "Europe's Plagues Came From China, Study Finds". The New York Times . Retrieved November 1, 2010.
  9. Morelli, G.; Song, Y.; Mazzoni, C.J.; Eppinger, M.; Roumagnac, P.; Wagner, D.M.; Feldkamp, M.; Kusecek, B.; Vogler, A.J.; Li, Y.; Cui, Y.; Thomson, N.R.; Jombart, T.; Leblois, R.; Lichtner, P.; Rahalison, L.; Petersen, J.M.; Balloux, F.; Keim, Pl; Wirth, T.; Ravel, J.; Yang, R.; Carniel, E.; Achtman, M. (December 2010). "Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity". Nature Genetics. 42 (#12): 1140–1143. doi:10.1038/ng.705. PMC   2999892 . PMID   21037571.
  10. Zhang, Sarah, "An Ancient Case of the Plague Could Rewrite History", The Atlantic, December 6, 2018
  11. Bockemühl J (1994). "100 years after the discovery of the plague-causing agent – importance and veneration of Alexandre Yersin in Vietnam today". Immun Infekt. 22 (#2): 72–75. PMID   7959865.
  12. Howard-Jones N (1973). "Was Kitasato Shibasaburō the discoverer of the plague bacillus?". Perspect Biol Med. 16 (#2): 292–307. doi:10.1353/pbm.1973.0034. PMID   4570035.
  13. 1 2 CDC, "The Plague", Centers for Disease Control and Prevention, Oct. 2017 PD-icon.svgThis article incorporates text from this source, which is in the public domain.
  14. 1 2 Collins FM (1996). Baron S; et al. (eds.). Pasteurella, Yersinia, and Francisella. In: Baron's Medical Microbiology (4th ed.). Univ. of Texas Medical Branch. ISBN   978-0-9631172-1-2.
  15. Stackebrandt, Erko; Dworkin, Martin; Falkow, Stanley; Rosenberg, Eugene; Karl-Heinz Schleifer (2005). The Prokaryotes: A Handbook on the Biology of Bacteria: Volume 6: Proteobacteria: Gamma Subclass. Berlin: Springer. ISBN   978-0-387-25499-9.
  16. Deng, W.; Burland, V.; Plunkett III, G.; Boutin, A.; Mayhew, G.F.; Liss, P.; Perna, N.T.; Rose, D.J.; Mau, B.; Zhou, S.; Schwartz, D.C.; Fetherston, J.D.; Lindler, L.E.; Brubaker, R.R.; Plano, G.V.; Straley, S.C.; McDonough, K.A.; Nilles, M.L.; Matson, J.S.; Blattner, F.R.; Perry, R.D. (August 2002). "Genome sequence of Yersinia pestis KIM". Journal of Bacteriology. 184 (#16): 4601–4611. doi:10.1128/JB.184.16.4601-4611.2002. PMC   135232 . PMID   12142430.
  17. Parkhill, J.; Wren, B.W.; Thomson, N.R.; Titball, R.W.; Holden, H.T.; Prentice, M.B.; Sebaihia, M.; James, K.D.; Churcher, C.; Mungall, K.L.; Baker, S.; Basham, D.; Bentley, S.D.; Brooks, K.; Cerdeño-Tárraga, 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.; Barrell, B.G. (October 2001). "Genome sequence of Yersinia pestis, the causative agent of plague". Nature. 413 (#6, 855): 523–527. Bibcode:2001Natur.413..523P. doi:10.1038/35097083. PMID   11586360.
  18. Chain PS, Hu P, Malfatti SA, et al. (2006). "Complete Genome Sequence of Yersinia pestis Strains Antiqua and Nepal 516: Evidence of Gene Reduction in an Emerging Pathogen". J. Bacteriol. 188 (#12): 4453–4463. doi:10.1128/JB.00124-06. PMC   1482938 . PMID   16740952.
  19. 1 2 Hinnebusch BJ, Rudolph AE, Cherepanov P, Dixon JE, Schwan TG, Forsberg A (2002). "Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector". Science. 296 (#5, 568): 733–735. Bibcode:2002Sci...296..733H. doi:10.1126/science.1069972. PMID   11976454.
  20. 1 2 Lathem WW, Price PA, Miller VL, Goldman WE (2007). "A plasminogen-activating protease specifically controls the development of primary pneumonic plague". Science. 315 (#5, 811): 509–513. Bibcode:2007Sci...315..509L. doi:10.1126/science.1137195. PMID   17255510.
  21. Hixson, K.K.; Adkins, J.N.; Baker, S.E.; Moore, R.J.; Chromy, B.A.; Smith, R.D.; McCutchen-Maloney, S.L.; Lipton, M.S. (November 2006). "Biomarker candidate identification in Yersinia pestis using organism-wide semiquantitative proteomics". Journal of Proteome Research. 5 (#11): 3008–3017. doi:10.1021/pr060179y. PMID   17081052.
  22. Schiano, Chelsea A.; Koo, Jovanka T.; Schipma, Matthew J.; Caulfield, Adam J.; Jafari, Nadereh; Lathem, Wyndham W. (2014-05-01). "Genome-wide analysis of small RNAs expressed by Yersinia pestis identifies a regulator of the Yop-Ysc type III secretion system". Journal of Bacteriology. 196 (#9): 1659–1670. doi:10.1128/JB.01456-13. ISSN   1098-5530. PMC   3993326 . PMID   24532772.
  23. Cornelis, G. R.; Boland, A.; Boyd, A. P.; Geuijen, C.; Iriarte, M.; Neyt, C.; Sory, M. P.; Stainier, I. (1998-12-01). "The virulence plasmid of Yersinia, an antihost genome". Microbiology and Molecular Biology Reviews. 62 (#4): 1315–1352. ISSN   1092-2172. PMC   98948 . PMID   9841674.
  24. Yan, Yanfeng; Su, Shanchun; Meng, Xiangrong; Ji, Xiaolan; Qu, Yi; Liu, Zizhong; Wang, Xiaoyi; Cui, Yujun; Deng, Zhongliang (2013). "Determination of sRNA expressions by RNA-seq in Yersinia pestis grown in vitro and during infection". PLOS ONE. 8 (#9): e74495. Bibcode:2013PLoSO...874495Y. doi:10.1371/journal.pone.0074495. ISSN   1932-6203. PMC   3770706 . PMID   24040259.
  25. Meyer K.F. (1957). "The natural history of plague and psittacosis: The R. E. Dyer Lecture". Public Health Reports. 72 (#8): 705–719. doi:10.2307/4589874. JSTOR   4589874. PMC   2031327 . PMID   13453634.
  26. von Reyn CF, Weber NS, Tempest B, et al. (1977). "Epidemiologic and clinical features of an outbreak of bubonic plague in New Mexico". J. Infect. Dis. 136 (#4): 489–494. doi:10.1093/infdis/136.4.489. PMID   908848.
  27. Pauli JN, Buskirk SW, Williams ES, Edwards WH (2006). "A plague epizootic in the black-tailed prairie dog (Cynomys ludovicianus)". J. Wildl. Dis. 42 (#1): 74–80. doi:10.7589/0090-3558-42.1.74. PMID   16699150.
  28. Webb CT, Brooks CP, Gage KL, Antolin MF (2006). "Classic flea-borne transmission does not drive plague epizootics in prairie dogs". Proc. Natl. Acad. Sci. USA. 103 (#16): 6236–6241. Bibcode:2006PNAS..103.6236W. doi:10.1073/pnas.0510090103. PMC   1434514 . PMID   16603630.
  29. Bertherat, E.; Bekhoucha, S.; Chougrani, S.; Razik, F.; Duchemin, J.B.; Houti, L.; Deharib, L.; Fayolle, C.; Makrerougrass, B.; Dali-Yahia, R.; Bellal, R.; Belhabri, L.; Chaieb, A.; Tikhomirov, E.; Carniel, E. (October 2007). "Plague reappearance in Algeria after 50 years, 2003". Emerging Infectious Diseases. 13 (#10): 1459–1462. doi:10.3201/eid1310.070284. PMC   2851531 . PMID   18257987.
  30. "Cats – Healthy Pets Healthy People". Centers for Disease Control and Prevention. 2016-05-13. Retrieved 2016-11-25.
  31. Zhou D, Han Y, Yang R (2006). "Molecular and physiological insights into plague transmission, virulence and etiology". Microbes Infect. 8 (#1): 273–284. doi:10.1016/j.micinf.2005.06.006. PMID   16182593.
  32. B.J. Hinnebusch; R.D. Perry & T.G. Schwan (1996). "Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas". Science. 273 (#5, 237): 367–370. Bibcode:1996Sci...273..367H. doi:10.1126/science.273.5273.367. PMID   8662526.
  33. Erickson, D. L.; N. R. Waterfield; V. Vadyvaloo; D. Long; E. R. Fischer; R. Ffrench-Constant & B. J. Hinnebusch (2007). "Acute oral toxicity of Yersinia pseudotuberculosis to fleas: Implications for the evolution of vector-borne transmission of plague". Cellular Microbiology. 9 (#11): 2658–2666. doi:10.1111/j.1462-5822.2007.00986.x. PMID   17587333.
  34. Hinnebusch, B. J.; Erickson, D. L. (2008). "Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague". Current Topics in Microbiology and Immunology. 322: 229–248. doi:10.1007/978-3-540-75418-3_11. ISBN   978-3-540-75417-6. ISSN   0070-217X. PMC   3727414 . PMID   18453279.
  35. Hinnebusch, B. J.; Erickson, D. L. (2008). "Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague". Current Topics in Microbiology and Immunology. 322: 229–248. doi:10.1007/978-3-540-75418-3_11. ISBN   978-3-540-75417-6. ISSN   0070-217X. PMC   3727414 . PMID   18453279.
  36. Salyers AA, Whitt DD (2002). Bacterial Pathogenesis: A Molecular Approach (2nd ed.). ASM Press. pp. 207–212.
  37. Viboud GI, Bliska JB (2005). "Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis". Annu. Rev. Microbiol. 59 (#1): 69–89. doi:10.1146/annurev.micro.59.030804.121320. PMID   15847602.
  38. de la Puerta ML, Trinidad AG, del Carmen Rodríguez M, Bogetz J, Sánchez Crespo M, Mustelin T, Alonso A, Bayón Y (February 2009). Bozza P (ed.). "Characterization of New Substrates Targeted By Yersinia Tyrosine Phosphatase YopH". PLoS ONE. 4 (#2): e4431. Bibcode:2009PLoSO...4.4431D. doi:10.1371/journal.pone.0004431. PMC   2637541 . PMID   19221593.
  39. Mejía E, Bliska JB, Viboud GI (February 2009). "Yersinia Controls Type III Effector Delivery into Host Cells by Modulating Rho Activity". PLoS ONE. 4 (#2): e4431. doi:10.1371/journal.ppat.0040003. PMC   2186360 . PMID   18193942.
  40. Hao YH, Wang Y, Burdette D, Mukherjee S, Keitany G, Goldsmith E, Orth K (January 2008). Kobe B (ed.). "Structural Requirements for Yersinia YopJ Inhibition of MAP Kinase Pathways". PLoS ONE. 3 (#1): e1375. Bibcode:2008PLoSO...3.1375H. doi:10.1371/journal.pone.0001375. PMC   2147050 . PMID   18167536.
  41. Mukherjee, S.; Keitany, Gladys; Li, Yan; Wang, Yong; Ball, Haydn L.; Goldsmith, Elizabeth J.; Orth, Kim (2006). "Yersinia YopJ Acetylates and Inhibits Kinase Activation by Blocking Phosphorylation". Science. 312 (#5, 777): 1211–1214. Bibcode:2006Sci...312.1211M. doi:10.1126/science.1126867. PMID   16728640.
  42. Mittal, R.; Peak-Chew, S.-Y.; McMahon, H. T. (2006). "Acetylation of MEK2 and I B kinase (IKK) activation loop residues by YopJ inhibits signaling". Proceedings of the National Academy of Sciences. 103 (#49): 18574–18579. Bibcode:2006PNAS..10318574M. doi:10.1073/pnas.0608995103. PMC   1654131 . PMID   17116858.
  43. Mittal R, Peak-Chew SY, Sade RS, Vallis Y, McMahon HT (2010). "The Acetyltransferase Activity of the Bacterial Toxin YopJ of Yersinia Is Activated by Eukaryotic Host Cell Inositol Hexakisphosphate". J Biol Chem. 285 (#26): 19927–19934. doi:10.1074/jbc.M110.126581. PMC   2888404 . PMID   20430892.
  44. Park H, Teja K, O'Shea JJ, Siegel RM (May 2007). "The Yersinia effector protein YpkA induces apoptosis independently of actin depolymerization". J. Immunol. 178 (#10): 6426–6434. doi:10.4049/jimmunol.178.10.6426. PMID   17475872.
  45. 1 2 Kelly, John (2005). Great mortality : an intimate history of the Black Death (1st ed.). London [u.a.]: Fourth Estate. p. 35. ISBN   978-0007150694.
  46. Welkos S, et al. (2002). "Determination of the virulence of the pigmentation-deficient and pigmentation-/plasminogen activator-deficient strains of Yersinia pestis in non-human primate and mouse models of pneumonic plague". Vaccine. 20 (17–18): 2206–2214. doi:10.1016/S0264-410X(02)00119-6. PMID   12009274.
  47. Pitt ML (13 October 2004). Non-human primates as a model for pneumonic plague (PDF). Animals Models and Correlates of Protection for Plague Vaccines Workshop, Gaithersburg, Maryland. Center for Biologics Evaluation and Research (Food and Drug Administration, Department of Health and Human Resources). pp. 222–248. Archived from the original (PDF) on 25 December 2019.
  48. Jefferson T, Demicheli V, Pratt M (2000). Jefferson T (ed.). "Vaccines for preventing plague". Cochrane Database Syst Rev (1): CD000976. doi:10.1002/14651858.CD000976. ISSN   1465-1858. PMC   6532692 . PMID   10796565. Art. No. CD000976.
  49. "The Plague". Association Amicale Sante Navale et d'Outremer. Archived from the original on 4 September 2012.
  50. "On This Day: San Francisco Bubonic Plague Outbreak Begins". Finding Dulcinea. Retrieved 2017-11-25.
  51. Chase, M. (2004). The Barbary Plague: The Black Death in Victorian San Francisco. Random House Trade Paperbacks.
  52. Rascovan, Nicolas, et al, Emergence and Spread of Basal Lineages of Yersinia pestis during the Neolithic Decline , Cell, December 6, 2018, doi : 10.1016/j.cell.2018.11.005
  53. 1 2 Rasmussen, Simon; Allentoft, Morten Erik; Nielsen, Kasper; Orlando, Ludovic; Sikora, Martin; Sjögren, Karl-Göran; Pedersen, Anders Gorm; Schubert, Mikkel; Van Dam, Alex; Kapel, Christian Moliin Outzen; Nielsen, Henrik Bjørn; Brunak, Søren; Avetisyan, Pavel; Epimakhov, Andrey; Khalyapin, Mikhail Viktorovich; Gnuni, Artak; Kriiska, Aivar; Lasak, Irena; Metspalu, Mait; Moiseyev, Vyacheslav; Gromov, Andrei; Pokutta, Dalia; Saag, Lehti; Varul, Liivi; Yepiskoposyan, Levon; Sicheritz-Pontén, Thomas; Foley, Robert A.; Lahr, Marta Mirazón; Nielsen, Rasmus; Kristiansen, Kristian; Willerslev, Eske (2015). "Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago". Cell. 163 (#3): 571–582. doi:10.1016/j.cell.2015.10.009. ISSN   0092-8674. PMC   4644222 . PMID   26496604. CC-BY icon.svg This article contains quotations from this source, which is available under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
  54. 1 2 3 Spyrou, Maria A.; Tukhbatova, Rezeda I.; Wang, Chuan-Chao; a; Lankapalli, Aditya K.; Kondrashin, Vitaly V.; Tsybin, Victor A.; Khokhlov, Aleksandr; hnert; Herbig, Alexander; Bos, Kirsten I.; Krause, Johannes (2018-06-08). "Analysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague". Nature Communications. 9 (#1): 2234. Bibcode:2018NatCo...9.2234S. doi:10.1038/s41467-018-04550-9. ISSN   2041-1723. PMC   5993720 . PMID   29884871. CC-BY icon.svg This article contains quotations from this source, which is available under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
  55. Achtman, M; Zurth, K; Morelli, G; Torrea, G; Guiyoule, A; Carniel, E (1999). "Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis". Proc Natl Acad Sci USA. 96 (#24): 14043–14048. Bibcode:1999PNAS...9614043A. doi:10.1073/pnas.96.24.14043. PMC   24187 . PMID   10570195.
  56. Jarrett, CO; Deak, E; Isherwood, KE; Oyston, PC; Fischer, ER; Whitney, AR; Kobayashi, SD; DeLeo, FR; Hinnebusch, BJ (2004). "Transmission of Yersinia pestis from an infectious biofilm in the flea vector". J Infect Dis. 190 (#4): 783–792. doi:10.1086/422695. PMID   15272407.
  57. Erickson DL1, Jarrett CO; Wren, BW; Hinnebusch, BJ (2006). "Serotype differences and lack of biofilm formation characterize Yersinia pseudotuberculosis infection of the Xenopsylla cheopis flea vector of Yersinia pestis". J Bacteriol. 188 (#3): 1113–1119. doi:10.1128/jb.188.3.1113-1119.2006. PMC   1347331 . PMID   16428415.
  58. Derbise, A; Chenal-Francisque, V; Pouillot, F; Fayolle, C; Prévost, MC; Médigue, C; Hinnebusch, BJ; Carniel, E (2007). "A horizontally acquired filamentous phage contributes to the pathogenicity of the plague bacillus". Mol Microbiol. 63 (#4): 1145–1157. doi:10.1111/j.1365-2958.2006.05570.x. PMID   17238929.
  59. Sadovi, Carlos (2009-09-19). "U. of C. researcher dies after exposure to plague bacteria". Chicago Breaking News Center. Retrieved 2010-03-03.
  60. Randall, Tom (Feb 25, 2011). "Plague Death Came Within Hours, Spurred by Scientist's Medical Condition".
  61. Haensch S, Bianucci R, Signoli M, Rajerison M, Schultz M, Kacki S, Vermunt M, Weston DA, Hurst D, Achtman M, Carniel E, Bramanti B (2010). "Distinct Clones of Yersinia pestis Caused the Black Death". PLoS Pathogens. 6 (#10): e1001134. doi:10.1371/journal.ppat.1001134. PMC   2951374 . PMID   20949072.
  62. Bos KI, Schuenemann VJ, Golding GB, Burbano HA, Waglechner N, Coombes BK, McPhee JB, DeWitte SN, Meyer M, Schmedes S, Wood J, Earn DJ, Herring DA, Bauer P, Poinar HN, Krause J (12 October 2011). "A draft genome of Yersinia pestis from victims of the Black Death". Nature. 478 (7370): 506–10. Bibcode:2011Natur.478..506B. doi:10.1038/nature10549. PMC   3690193 . PMID   21993626.
  63. Rasmussen, Simon; Allentoft, Morten Erik; Nielsen, Kasper; Orlando, Ludovic; Sikora, Martin; Sjögren, Karl-Göran; Pedersen, Anders Gorm; Schubert, Mikkel; Van Dam, Alex; Kapel, Christian Moliin Outzen; Nielsen, Henrik Bjørn; Brunak, Søren; Avetisyan, Pavel; Epimakhov, Andrey; Khalyapin, Mikhail Viktorovich; Gnuni, Artak; Kriiska, Aivar; Lasak, Irena; Metspalu, Mait; Moiseyev, Vyacheslav; Gromov, Andrei; Pokutta, Dalia; Saag, Lehti; Varul, Liivi; Yepiskoposyan, Levon; Sicheritz-Pontén, Thomas; Foley, Robert A.; Lahr, Marta Mirazón; Nielsen, Rasmus; et al. (2015). "Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago". Cell. 163 (#3): 571–582. doi:10.1016/j.cell.2015.10.009. PMC   4644222 . PMID   26496604.
  64. "DNA of bacteria responsible for London Great Plague of 1665 identified for first time".
  65. "Don't blame the rats: Human fleas and lice likely spread Black Death". CBC News.
  66. Dean, Katharine R; Krauer, Fabienne; Walløe, Lars; Lingjærde, Ole Christian; Bramanti, Barbara; Stenseth, Nils Chr; Schmid, Boris V (2018). "Human ectoparasites and the spread of plague in Europe during the Second Pandemic". Proceedings of the National Academy of Sciences. 115 (#6): 1304–1309. doi:10.1073/pnas.1715640115. PMC   5819418 . PMID   29339508.