Persistent Survival of Plague Linked to Individual Gene Across Ages
Historian Bacteria: Single Gene Adaptation Revealed as Key to Plague's Resilience for Centuries
The plague, responsible for the deadliest pandemic in human history, has intrigued scientists for centuries. The bacterium that causes the plague, Yersinia pestis, has thrived for millennia, causing devastating outbreaks across the ages.
In a groundbreaking discovery, researchers have pinpointed a genetic factor that facilitated the plague's long-term survival—adaptive changes in a single gene. The findings were published Thursday (May 29) in the journal Science.
"We've taken a closer look at the DNA of the plague bacterium across time and space, seeking clues about what drives its persistence, virulence, and whether it has the potential to re-emerge as a deadly pandemic," explained co-senior author Hendrik Poinar, director of the Ancient DNA Centre at McMaster University in Ontario, Canada.
Y. pestis has been infecting humans since before documented history began, with the most common form, bubonic plague, typically transmitted through bites from infected fleas. However, direct contact with infected animals, including rats and cats, can also transmit the disease. Once inside the body, the bacterium travels to lymph nodes, replicating and causing painful, pus-filled "buboes."
The plague bacterium can also cause blood infections (septicemic plague) and lung infections (pneumonic plague).
Outbreaks of the plague-including the Justinian Plague (which occurred roughly between A.D. 542 and 750), the infamous 14th-century Black Death, and the 1855 global plague pandemic that began in China's Yunnan province-have claimed tens of millions of lives. Plague epidemics persist to this day, with endemic countries such as the Democratic Republic of the Congo, Madagascar, and Peru accounting for most of them.
What makes the plague so remarkable is its strain longevity. Strains of the Justinian Plague bacterium took 300 years to fade after outbreaks were first documented, and one of the two lineages from the Black Death resurfaced in waves for 500 years before disappearing, while the other became the ancestor of all present-day strains.
To investigate the genetic toolkit that Y. pestis uses to persist for so long, researchers examined a plague gene, pla, across hundreds of samples collected from ancient and modern victims of the disease.
The pla gene codes for an enzyme that allows the plague bacterium to evade the host's immune system. Previous studies suggested that pla is a key factor in modulating the lethality of a given plague strain and its ability to spark outbreaks in humans, but one plague strain can carry a varying number of pla genes. In their study, researchers found that the number of pla copies was related to disease severity and transmission potential.
By comparing the number of pla genes in plague strains taken from ancient and modern victims of the plague, the researchers noted a pattern where the plague strains lost copies of pla over time. The scientists hypothesized that this adaptation likely made infections less virulent, or harmful to the host's body, over time, which would help the disease to spread more widely.
"Our findings shed light on how the plague bacterium has survived and adapted over centuries, and we believe that further research into both ancient and contemporary plague strains could reveal more about the genetic factors that have shaped its virulence and transmission potential," said Poinar.
Nowadays, Y. pestis infections can be treated with antibiotics, although some strains have shown troubling signs of antibiotic resistance. In the United Kingdom, scientists have already started developing a bubonic plague vaccine to add to stockpiles in an effort to head off the threat of a superbug plague outbreak.
The study on the plague bacterium's persistence suggests that adaptive changes in the pla gene, which codes for an immune-evading enzyme, have played a significant role in chronic diseases like the plague, as the number of pla copies was found to be related to disease severity and transmission potential. Furthermore, the findings in health and wellness research indicate that the plague strains have lost copies of the pla gene over time, which may have contributed to the development of medical conditions such as less virulent infections, potentially enhancing the plague's ability to spread.
