Bubonic plague has caused the deadliest pandemic in history: The Black Death, which killed as many as 50% of affected populations in Western Asia, Africa, and Europe. After that, in the 14th century, there were waves of bubonic plague pandemics over the next 500 years until about 1840. The bacterium that causes bubonic plague, known as Yersinia pestis can cause severe illness and death. Now reporting in Science, researchers have shown how one gene in the Yersinia pestis genome has enabled its survival over hundreds of years, with tweaks to virulence and deadliness. Now, outbreaks still occur in some regions, but they are controlled with antibiotics.
"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," explained co-senior study author Hendrik Poinar, director of the McMaster Ancient DNA Center and Chair of Genetic Anthropology.
The first bubonic plague pandemic happened in the mid-500s, and is known as the Plague of Justinian. The second was the Black Death, from 1346 to 1353. The third pandemic of bubonic plague started in China in 1855 and the World Health Organization declared it over in 1960. But there are still some infections in a few countries such as Madagascar and the Democratic Republic of Congo.
Bacterial strains that led to the Justinian plague died out after about 300 years of tearing through populations in Europe and the Middle East. The Black Death, the second plague pandemic, was caused by rodents carrying the bacteria. Because of their high reproductive numbers and proximity to humans, rodents likely were a kind of amplifier for transmission.
The bacteria that caused the second plague split into two lineages. Modern day strains are all descended from one of these lineages, while the other went extinct in the 19th century.
In this study, the researchers looked for a gene known as pla, which is highly expressed by Y pestis, and helps the pathogen remain undetected by the immune system as it moves to the lymph nodes and then the rest of the body. The team found this gene in hundreds of samples, and revealed the total number of pla genes carried by Y pestis over time.
This showed that the number of pla genes was dynamic; there were fewer copies in later outbreaks, which lowered mortality by about 20% and lengthened the infection. Hosts could survive for longer periods before they died. But in earlier pandemics with Y. pestis strains carrying higher number of pla genes, death was faster and more likely.
"The reduction of pla may reflect the changing size and density of rodent and human populations," suggested Poinar. "It's important to remember that the plague was an epidemic of rats, which were the drivers of epidemics and pandemics. Humans were accidental victims."
Modern and ancient strains of Y. pestis were also found to evolve in very similar ways, with pla reductions happening as time went on. As this gene copy number was reduced and hosts survived longer, the disease also had more chance to spread.
Luckily for us, modern strains are typically controlled with antibiotics. But this study can help us learn more about how pathogens spread.
Sources: McMaster University, Science
