For the first time, researchers have sequenced the full genome of the bacterium that caused a plague that killed millions of people in the 6th century A.D., and discovered to their surprise that the outbreak was caused by a different strain of the same germ that was to blame for the more famous Black Death 800 years later. Their findings offer insight into the genetic factors that influence the virulence of the plague bacterium as well as other pathogens.



Estimates vary for the number of people killed by the plague during the so-called Black Death that ravaged Europe from 1347 to 1351. But the number was certainly in the tens of millions; it is thought that as much as half of the entire European population at the time may have been killed by Yersinia pestis, the bacterium that causes the plague.



Almost exactly 800 years before the Black Death another plague pandemic swept through what was then the Eastern Roman, or Byzantine, Empire, reaching its peak in its capital Constantinople (present-day Istanbul) around A.D. 541. It is known as the Plague of Justinian, named for the Byzantine emperor at the time. Again, mortality estimates vary, but were likely also in the tens of millions, with one contemporary account estimating that as many as 100 million people had died.



Scientists had determined fairly recently that both the Plague of Justinian and the Black Death were caused by the bacterium Y. pestis, and the full genome of the Black Death strain had been sequenced in 2011. But they didn’t know whether both pandemics were caused by the same strain or different strains of the bacterium. To find out, a group of researchers extracted the pathogen’s DNA from the tooth of one of the Byzantine plague’s long-buried victims. They published their findings online January 27th in The Lancet Infectious Diseases. Co-author Hendrik Poinar, professor at McMaster University in Ontario, says he was surprised by the results; he had expected that both pandemics were caused by the same strain.



“In my mind, pretty much all plague [Y. pestis] strains around the world are capable of causing human disease, and if conditions were right, would probably be capable of causing these large pandemics again,” says David Wagner, professor at Northern Arizona University in Flagstaff and the lead author of the paper. The fact that there were two separate strains that jumped from rats and fleas (which are the usual hosts of the plague bacterium) to humans, causing massive pandemics, underlines the virulence of the Y. pestis bacterium, he says.



But although the bacterium may be biologically capable of causing another pandemic, Wagner doesn’t think that there’s much of a chance of that happening. “What’s changed is not the organism. What’s changed is humans and human condition,” he says. “Hygiene has improved immensely … you don’t just have rats all over the place like you might have had during the time of the major pandemics.” The second reason: antibiotics. “Plague is highly susceptible to simple antibiotics,” Wagner says.



Although this is good news for people living in developed countries, the bacterium is still responsible for thousands of deaths every year in developing countries like Madagascar and Uganda. “A lot of times these conditions in these developing countries aren’t much different, probably, from what the conditions were back during the first two pandemics,” says Ken Gage, a plague researcher at the U.S. Centers for Disease Control and Prevention who was not involved in the study. In Madagascar, for example, “the black rat is found throughout the island,” Wagner notes.



The researchers had also hoped to find clues in the Y. pestis genome as to what made this particular strain cause a pandemic that killed millions, whereas other strains have had no such effect on humans. But although they found some genes that might make this strain more virulent, “there are no smoking guns,” Wagner says.



Poinar points out, however, that even the small changes in some regions of the pathogen’s genome “can cause a tremendous physiological effect.” He points out one particular region of the genome “that has some interesting virulence functions on it.” The next step of the research, he says, is isolating those different genes that may be responsible for increased virulence and testing them in controlled settings on rodents.

