A strain of bubonic plague as deadly as the one that caused the Black Death could make a reappearance on Earth, scientists have warned.
The evidence comes from research into one of the most devastating pandemics in human history, the Plague of Justinian, which killed half the world's population.
Scientists who isolated genetic traces of the plague from the teeth of two 1,500-year-old victims found it was caused by a distinctly different bacterial strain from that responsible for the later Black Death.
Both scourges were triggered by the bubonic plague bug Yersinia pestis, which can be spread from rats to humans by fleas.
The new research shows that the two infectious organisms were distinct strains. While the Justinian strain vanished from the Earth, the Black Death strain gave rise to another pandemic in the late 1800s.
The discovery suggests that a new deadly strain of plague could strike again without warning.
"We know the bacterium Y. pestis has jumped from rodents into humans throughout history and rodent reservoirs of plague still exist today in many parts of the world," said Dr Dave Wagner, a member of the international team of scientists from Northern Arizona University in the US.
"If the Justinian plague could erupt in the human population, cause a massive pandemic, and then die out, it suggests it could happen again. Fortunately we now have antibiotics that could be used to effectively treat plague, which lessens the chances of another large-scale human pandemic."
The Plague of Justinian struck in the 6th century and is estimated to have killed between 30 million and 50 million people as it spread across Asia, North Africa, the Middle East and Europe - virtually half the world's population at the time.
Some 800 years later, the Black Death wiped out 50 million Europeans between 1347 and 1351.
The scientists managed to recover tiny DNA fragments of the bacterium from the teeth of two Justinian plague victims buried in Bavaria, Germany.
From these short remnants they reconstructed the genome of the Justinian strain of Y. pestis and compared it with a database of more than 100 contemporary strains.
The findings, published online in the journal The Lancet Infectious Diseases, revealed that the strain responsible for the Justinian plague was an evolutionary "dead end". It came, did its damage, and disappeared from the Earth, having no connection with the later Black Death.
The 19th century pandemic which spread across the globe from Hong Kong was a likely descendent of the more successful Black Death strain, said the scientists.
Experts now think the Justinian strain of Y. pestis originated in Asia, not in Africa as originally thought.
But there was no molecular evidence of a link with earlier smaller epidemics such as the Plague of Athens in 430 BC and the Antonine Plague between the years 165 and 180.
These outbreaks could also represent separate, independent emergences of Y. pestis strains capable of infecting humans, it is believed.
"This study raises intriguing questions about why a pathogen that was both so successful and so deadly died out," said Australian co-author Dr Edward Holmes, from the University of Sydney. "One testable possibility is that human populations evolved to become less susceptible."
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