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How Yersinia bacteria cause disease in humans
human flea, a specimen collected in Spain in the 1890s, which had been sitting in alcohol for more than a century in the Entomology Museum in Cambridge the colour is autofluorescence in the exoskeleton, from which all soft tissues have been removed with alkali. Picture courtesy of Brad Amos, LMB
Human flea (photo: Brad Amos, MRC-LMB)

The Black Death was one of the worst natural disasters in history. In 1347 A.D. one third of the population of Europe died as the plague swept through. The first indications of the plague in London was the widespread cases of rats dying in large numbers. They were infected with fleas which carried highly infectious bacteria of the Yersinia species. These fleas can turn to humans as a food source and transmit the bacteria which in turn can infect human fleas and so transmit the disease from human to human.

Rat flea (photo WHO)

Yersinia bacteria multiply in humans and inject toxins into cells, making the host unable to fight the infection (see below). Today antibiotics can kill these bacteria and thus sporadic cases of the plague are rare and will remain thus as long as antibiotic resistant strains do not become prevalent. Currently most cases of human plague are acquired by flea bites, with other cases caused by handling infected animals.

Evil Yersinia injecting his cocktail of toxins into our cells to dampen innate immunity
Mechanisms by which Yersinia infects and spreads in humans

Different strains of Yersinia bacteria manifest themselves with different symptoms. Yersinia pestis are bacteria that can infect human lymph nodes which leads to discoloured swelling called buboes (bubonic plague). This infection can spread internally by the bloodstream to the lungs or can enter the lungs through inhalation of bacteria in airborne water droplets (pneumonic plague, which shows rapid mortality). Yersinia pestis can also lead to the black plague where the bacteria enters the victim's blood and causes a septic shock (this form of the disease is alternatively called septicemic plague and shows rapid mortality), where discolouration of the skin is due to coagulation of blood. Another strain, Yersinia entercolitica, enters through the gut and travels to the lymph nodes.

Yersinia attack cells particularly of the immune system, crippling them by injection toxins right across the cell membrane using an injection apparatus, called a Type III Secretion System. The six toxins injected are called Yops (Yersinia Outer membrane Proteins).

Type III Secretion system of Yersinia

These Yop toxins disable host cells from engulfing the bacteria and digesting them. They also disable an innate immune response of human cells and they also affect cell adhesion.

Yop Toxins

Toxic activities of Yersinia Yop proteins
Cell activities of Yersinia Yop toxins

Our work has uncovered how YopJ disables the innate immune response of human cells allowing the Yersinia to proliferate.

acetylation of MEK1 by YopJ Yersinia toxin

YopJ is primarily responsible for inactivating innate immune responses in macrophages, dendritic cells and neutrophils allowing the bacteria to survive and multiply in the body. This first line of defense is very important in being able to cope with infections and it is of great importance to know how Yersinia can target the appropriate cells and subvert their immune responses. We have discovered how the later activity is controlled by YopJ.

Click here for our work on how Yop J works

RIng-A-Ring-of-Roses by Fredrick Morgan
by Fredrick Morgan

Ring a Ring O'Roses,

A pocketful of Posies

Atishoo! Atishoo!

We all fall down!

It is thought that this children's ditty originates from the time of the plague and explains what was perceived to happen

One of the first symptoms of the plague was a ring of red (rose) coloured spots

A posy of herbs was meant to protect against the disease

The victim sneezes and

falls down (dead)

Our publications on YopJ
Mittal et al PNAS 2006
Mittal et al JBC 2010

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