Scientists discover how a single gene shaped the course of the plague pandemic

Scientists discover how a single gene shaped the course of the plague pandemic

Scientists have documented the way a single gene in the bacterium that causes bubonic plague.Yersinia pestisallowed it to survive for hundreds of years by adjusting its virulence and the time it took to kill its victims, but these forms of plague eventually died out.

A study by researchers at McMaster University and France's Institut Pasteur published today in the journalScienceaddresses some fundamental questions about pandemics: How do they enter human populations, cause immense disease, and evolve different levels of virulence to persist in populations?

The Black Death remains the single deadliest pandemic in recorded human history, killing an estimated 30 to 50 percent of the populations of Europe, western Asia and Africa as it moved through those regions. In the 14th century it appeared in waves over more than 500 years and lasted until 1840.

The Black Death was caused by the same bacteria that caused Justinian's Plague, the first plague pandemic that broke out in the mid-500s. The third plague pandemic began in China in 1855 and continues today. Its deadly effects are now more controlled by antibiotics, but are still felt in regions such as Madagascar and the Democratic Republic of Congo, where cases are regularly reported.

This is one of the first research studies to directly examine changes in an ancient pathogen that we still see today, to understand what drives the virulence, persistence and/or eventual extinction of pandemics. “

Hendrik Poinar, co-senior author of the study, director of the McMaster Ancient DNA Center and Michael G. DeGroote Chair in Genetic Anthropology

The Justinian Plague tribes died after 300 years of ravaging European and Middle Eastern populations. Second pandemic strains emerged from infected rodent populations and caused the Black Death before breaking into two main lineages. One of these two lines is the ancestor of all modern tribes. The others were reintroduced into Europe over centuries and ultimately became extinct by the early 19th century.

Using hundreds of samples from ancient and modern plague victims, the team zeroed in on a gene known asPLA,a high copy component ofY. pestisThis helps move through the immune system undetected to the lymph nodes before spreading to the rest of the body.

Extensive genetic analysis revealed that their copy number or total numberPLAGenes found in the bacterium had decreased subsequent outbreaks of the disease, which in turn reduced mortality by 20 percent and increased the length of their infection, meaning the hosts lived longer before dying. These studies were conducted in mouse models of Bubonic Plague.

Vice versa, if thePLAGene was in its original, high copy number, the disease was much more virulent and killed every one of its hosts and did so much faster.

The scientists also identified a striking similarity between the trajectories of modern and ancient tribes, which evolved independentlyPLAIn the later stages of the first and second pandemics and so far in three samples of the third pandemic found in Vietnam today.

In both the Justinian and Black Death plagues, the evolutionary change occurred approximately 100 years after the initial outbreaks. Scientists suggest that as gene copy numbers fell and the infected rats lived longer, they were able to spread an infection further, ensuring the pathogen's reproductive success.

“The reduction ofPLAmay reflect the changing size and density of rodent and human populations," explains Poinar." It is important to note that plague was an epidemic of rats, which were the drivers of epidemics and pandemics. People were accidental victims. “

Black rats in cities likely acted as “amplification hosts” due to their high numbers and proximity to humans. Because black rats are very susceptible toY. pestisThe pathogen required rat populations to remain high enough to provide new hostsY. pestisPass and continue the pandemic cycle.

However, thePLA-The reduced strains eventually became extinct, likely reflecting a further shift in the host-pathogen relationship in their environment.

When researchers looked for signs of exhaustion in a large set of third pandemic samples in a collection at the Institut Pasteur, they found three contemporary strainsPLAExhaustion.

“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, similar to finding three rare needles in a haystack,” says Javier Pizarro-Cerdá, co-senior author of the work, Director of the Directorate of theYersiniaResearch unit and the WHO Collaboration Center for Pest at the Institut Pasteur.

The institute houses one of the richest modern collections in the worldY. pestisIsolate adds Guillem Mas Fiol, co-leader of the study and postdoctoral researcher who was supervised by Pizarro-Cerdá.

“One of the most interesting aspects of our research was the opportunity to study a trait that was first observed in extinct plague strains and could be experimentally tested for the first time in living contemporary bacterial strains,” he says.

“Although our research sheds light on an interesting pattern in the evolutionary history of plague, most of the strains circulating to this day in Africa, South America and India are those that were previously responsible for massive mortality,” says Ravneet Sidhu, co-lead author of the study and PHD candidate at the McMaster Ancient DNA Center.

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