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From stomach bug to blood-borne pathogen
The genome sequence of the plague bacterium
By Birgit Reinert

British researchers have sequenced the genome of Yersinia pestis, the bacterium that causes plague. The sequencing revealed a highly dynamic and adaptable pathogen that has undergone rapid genetic changes. It appears to have evolved in a remarkably short time from a relatively harmless stomach bug to a blood-borne pathogen.

The Plague by Arnold Böcklin (1827-1901). Painted in 1898, tempera. This painting was unfinished as the artist and his family twice had to flee cholera epidemics. The plague was known as 'Black Death' in the Middle Ages because symptoms included dark splotches under the skin.

As recently as 1,500 years ago, Y. pestis might have evolved from a much less harmful bacterium that infects the gut of humans and animals, Y. pseudotuberculosis. Over time, Y. pestis acquired genes from other bacteria and viruses that allowed it to live in the blood instead of the intestine. These include genes for insecticidal toxins—enabling the bacterium to parasitize fleas and leap from animals (rats) to humans. Altogether, the researchers identified 21 regions, or adaptation islands, that were probably acquired from other organisms.

Conversely, gene acquisition has been balanced by gene loss. The scientists revealed 149 deactivated genes, or pseudogenes, that once enabled Y. pestis to thrive in the human gut, but are no longer needed in the new environment. These include genes associated with adhesion, mobility and colonization of the gut.

"This genome sequence provides a unique insight into the genetic events that are associated with the emergence of a new pathogenic species," the researchers write in Nature. The three-year study, funded by the British Wellcome Trust, was led by Julian Parkhill of the Sanger Centre in Cambridge, UK.

The sequenced strain, known as Y. pestis strain CO92, has a chromosome of 4.65 million base pairs as well as three circular DNA molecules called plasmids. The sample was isolated from a veterinarian in Colorado, who died in 1992 of pneumonic plague after contracting the disease from an infected cat, which had sneezed on him.

Yersinia pestis is usually transmitted to humans by fleas that have fed on the blood of infected animals such as rats, causing bubonic plague in people. It is also transmitted by air through respiratory droplets, causing the more severe and often fatal pneumonic plague. If treated early enough though, antibiotics can prevent the disease from spreading to all the main organs including the lungs.

With the genome map in hand, the researchers expect to speed up research into vaccines and treatments. The annotated Y. pestis sequence is available from the Sanger Centre at

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Parkhill, J. et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413, 523-527 (October 4, 2001).

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