How the bubonic plague has survived for centuries

The catastrophic loss of life at the hands of a single bacterium during the 14th century remains one of human history’s most devastating events. Yersinia pestis–the bacterium that causes bubonic plague–managed to survive for centuries by adjusting its severity and the length of time it takes to kill its hosts. Despite that virulence, some forms of plague did ultimately die out. Now, scientists have documented the way that one single gene in Yersinia pestis made it so adaptable. The findings are described in a study published May 29 in the journal Science.

[ Related: Bubonic plague discovered in ancient Egyptian mummy DNA. ]

A crash course in plague

According to the Cleveland Clinic, there are three types of plague. Which type that you have depends on where in your body Yersinia pestis ends up. Bubonic plague infects the lymph nodes, septicemic plague is in the blood, and pneumonic plague affects the lungs.

Yersinia pestis itself is a bacterium with some deep historical roots and has caused three major pandemics in recorded human history. 

The Plague of Justinian in the mid-500s is the first recorded plague pandemic in human history. It is named for Justinian I, the Byzantine emperor at that time, and it devastated the Mediterranean region. Mortality estimates vary between 25 million and 100 million deaths. It killed roughly 40 percent of Constantinople’s (now Istanbul) population, which was the most important center of cultural and political life in the world. at the time.

It eventually led to the second plague pandemic–the Black Death in the 14th century. The Black Death is still the deadliest pandemic in recorded human history, killing 30 to 50 percent of the population in Europe, Western Asia, and Africa. The disease re-emerged in several waves over more than 500 years and persisted in that form until 1840.

The third plague pandemic began in China in 1855 and continues today. Antibiotics have significantly helped treat the disease, but its impacts are still felt in parts of Madagascar and the Democratic Republic of Congo, where cases are regularly reported.

Strains of the original Justinian plague went extinct after 300 years of wreaking havoc on European and Middle Eastern populations. The strains that caused the Black Death emerged from infected rodents before it broke into two major lineages. One of these two lineages is the ancestor of the present-day strains, while the other strain re-emerged over centuries in Europe and went extinct by the early 19th century.

“This is one of the first research studies to directly examine changes in an ancient pathogen, one we still see today, in an attempt to understand what drives the virulence, persistence and/or eventual extinction of pandemics,” Hendrik Poinar, a study co-author and molecular evolutionary geneticist and biological anthropologist at McMaster University in Canada, said in a statement.

The pla gene

In the new study, the team used hundreds of samples from ancient and modern plague victims. They screened the samples for a gene known as pla. This gene helps Yersinia pestis move through the body’s immune system undetected by the lymph nodes before it spreads to the rest of the body.

The genetic analysis revealed that its copy number–the total number of pla genes found in the bacterium–actually decreased in the later plague outbreaks. This decreased mortality by about 20 percent, while increasing the length of infection. The hosts typically lived longer before they died. These studies were performed in mice models of bubonic plague, according to the team.

When the pla gene was in its original, high copy number, the disease was much more virulent. It killed all of its hosts and did so much quicker.

Additionally, the team also pinpointed a similarity between the trajectories of both modern and ancient strains. These strains independently evolved similar reductions in the pla gene during the later stages of the first and second plague pandemics and in three samples from the third pandemic that were uncovered in present day Vietnam.

In both the Justinian plague from the 500s and the Black Death, the evolutionary change occurred approximately 100 years after the first outbreaks. The team believes that when the gene copy number dropped and the infected rats lived longer, the rodents could spread infection farther. This spread helped ensure the pathogen’s reproductive success.

“The reduction of pla may reflect the changing size and density of rodent and human populations,” explained Poinar. “It’s important to remember that plague was an epidemic of rats, which were the drivers of epidemics and pandemics. Humans were accidental victims.”

Due to their high numbers and proximity to humans, the black rats in cities likely acted as “amplification hosts.” Since these black rats are highly susceptible to Yersinia pestis themselves, the pathogen needed the rat populations to stay high enough to supply new hosts for Yersinia pestis to persist and allow the natural pandemic cycle to continue.

[ Related: DNA from plague victims’ teeth may unravel the origin of Black Death. ]

Finding ‘three rare needles in a haystack’

However, the strains of plague that did not have the pla gene eventually went extinct. This likely reflects another shift that occurred in the host-pathogen relationship within their environment.

When the team searched for signs of pla gene depletion in samples of the third plague pandemic preserved in a large collection at the Institut Pasteur in Paris, they found three contemporary strains with the pla depletion. The diminished virulence that the pathogen evolved in response to more of its hosts dying potentially caused these earlier plague pandemics to fizzle out.  

“Thanks to our international collaborators who monitor local epidemics of plague worldwide, we were able to find the unique bacterial samples used for this project, akin to finding of three rare needles in a haystack,” Javier Pizarro-Cerdá, a study co-author and microbiologist who specializes in plague at the Institut Pasteur, said in a statement.  

Despite this evolution, most of the strains circulating in some countries in Africa, South America, and Asia are more virulent. 

“Today, the plague is a rare disease, but one that remains a public health concern and serves as a model for gaining a broad understanding of how pandemics emerge and become extinct,” said Javier Pizarro-Cerdá. “This example illustrates the balance of virulence a pathogen can adopt in order to spread effectively from one host to another.”

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