By Paloma Salmeron-O’Brien
Yersinia pestis is a name that strikes fear into the hearts of scientists everywhere, but it could be just another Latin binomial to you. In fact, Y. pestis is the bacteria behind the Black Plague, which devastated 14th century Europe, killing an estimated 25 million people. Sound more familiar? Y. pestis is one of the most virulent pathogens known to infect humans and it has been responsible for numerous outbreaks in addition to the Black Death. The activity of this pathogen can be split into three major epidemics, which occurred from the 6th century to the 8th century, the 14th to the 18th, and the 19th century to the present (yes, Y. pestis is still kicking!). The second epidemic is a popular target for study due in part to the fact that the Black Death marks its beginning. But that’s not all that draws the interest of researchers.
While the plague itself has been widely discussed, its aftermath is a much less popular topic. The second epidemic lasted four centuries, which is an immense stretch of time to be dominated by one pathogen. Researchers from the University of Tübingen, Germany wanted to better understand just how Y. pestis managed to stick around to cause recurring outbreaks following the Black Death.
Studying Y. pestis and its evolutionary history is tricky business due to its high mutation rate. In order to understand the history of the strain that began the second epidemic, scientists compared sample strains from the second epidemic to both ancient and modern strains of Y. pestis. To procure the second epidemic samples, 50mg of dental pulp were removed from 20 teeth, which were freshly harvested from preserved plague victims. The victims perished in the Great Plague of Marseille in 1722, one of the last outbreaks in France during the second epidemic. The presence of Y. pestis DNA was determined using a PCR test for the gene pla, which denoted the presence of the pathogen. Five DNA extracts that came back positive for pla, and therefore for Y. pestis, were selected, each from a separate individual. These five samples were treated to remove damaged chemical components caused by age. The samples were then amplified, to increase the amount of genetic material for use, and sequenced. The reads were processed independently at three research facilities so findings could be pooled to ensure accuracy. To put these results into perspective, a phylogenetic tree was then constructed for Y. pestis using the maximum likelihood method, which assumes more simplistic lineages with fewer mutation events are likely to be more accurate. Various sections of the proposed ancestry were assessed for accuracy using additional sample sequencing.
Researchers found that these samples descended from the strain responsible for the Black Death, indicating that it was indeed the same Y. pestis lineage that maintained the course of the second epidemic. Furthermore, genetic analysis suggests that the lineage underwent adaptive radiation following the Black Death, leading to a boom of new Y. pestis strains. These many different strains, each with their own adaptations, would have been able to cause many outbreaks in combination. As the strains descending from the Black Death quickly mutated, the immune systems of Europeans would have been unable to keep up with the rapid disease adaptations, leaving them vulnerable to each new strain that came their way. This explains how the second epidemic persisted for so long but doesn’t yet reveal where the disease came from.
Y. pestis is a zoonotic disease, meaning it was spread from another animal - rats, in this case - to humans in what are referred to as spillover events. We know that the disease originated from rodent populations in Asia and was then transmitted through trade routes to Europe, so does the long life of the second epidemic trace back to constant trade? Actually, the study’s findings point instead to a local rodent reservoir in Europe, which kept the disease going. Once the disease spread from Asia through trade before the Black Plague, it established itself in European rodents, which lived among an ample supply of victims. The strains descending from the Black Death then had the opportunity to build genetic diversity within their host population. As more strains developed, they were able to freely cycle between rodents and humans to cause the subsequent outbreaks that made up the latter part of the second epidemic. It turns out the close proximity of the host rodent population to human victims played a significant role in allowing for the continuation of the epidemic.
The story of sustained plague uncovered by this study lends a very important lesson, even past the peak of Y. pestis’ influence. The ability of a disease to persist in a host population and adapt given time is not specific to Y. pestis. If given the opportunity, a disease will continue to colonize hosts, replicate, mutate, and eventually adapt to better colonize hosts and sustain this cycle. This is why the persistence of preventable diseases, such as Measles and Polio, are so dangerous. We have vaccines and other modern medical technology to foster immunity to these diseases and eradicate them from humankind. However, vaccine skepticism, hesitance, misinformation, and disinformation allow these diseases to remain and mutate, possibly beyond the bounds of our current vaccines. Thanks to the uncovered history of Y. pestis, we know what recurring disease looks like in the absence of modern medicine. All the more reason to read up on your history and have a little more faith in present science.
Bos, K. I., Herbig, A., Sahl, J., Waglechner, N., Fourment, M., Forrest, S. A., Klunk, J., Schuenemann, V. J., Poinar, D., Kuch, M., Golding, G. B., Dutour, O., Keim, P., Wagner, D. M., Holmes, E. C., Krause, J., & Poinar, H. N. (2016, January 21). Eighteenth Century yersinia pestis genomes reveal the long-term persistence of an historical plague focus. eLife. Retrieved December 6, 2021, from https://elifesciences.org/articles/12994#content.