A single, small genetic change in Yersinia pestis changed the course of human history, according to new research published in the journal Nature Communications. The acquisition of a single gene shifted this bacteria from causing a gastrointestinal infection to the fatal respiratory disease behind the Black Death.
Image credit: Northwestern University
The authors behind the new study, from Northwestern University Feinberg School of Medicine in Chicago, IL, analyzed ancient strains of Y. pestis to understand how the bacteria acquired the ability to infect the lungs, resulting in the pneumonic plague.
In the oldest of the Y. pestis strains that currently exist, the Northwestern team observed that although the bacteria can colonize the lungs, it cannot cause the severe disease associated with pneumonic plague.
Examining what differed in this ancestral strain, compared with other strains that do result in plague, the researchers identified the biggest change as being a gene for the surface protein Pla.
The authors suggest, therefore, that when the bacteria acquired this gene, its ability to infect the lungs was enhanced, resulting in the fatal lung infection familiar as pneumonic plague.
To test this theory, the Northwestern team inserted the Pla gene into the early ancestral strain of Y. pestis. Confirming the hypothesis, the addition of the gene resulted in the strain being able to cause respiratory infection identical to that caused by modern strains of the bacteria.
Although the bacteria has gained and lost genes over the last several thousand years, the researchers found that no other changes were required to transform the ancestral strain of Y. pestis into one capable of producing plague.
Looking more closely at the Pla gene, the team also found that a single modification to the gene allowed the bacteria to spread and infect the lymph nodes. This modification, found in modern strains of Y. pestis, causes the infection familiar as bubonic plague.
Based on these findings, the authors believe that Y. pestis evolved as a respiratory pathogen prior to its ability to cause bubonic plague, which is the most common form of the disease.
This theory overturns previous thinking on the evolution of Y. pestis, but the researchers claim this may explain how the bacteria went from causing just localized outbreaks of plague to history-changing pandemics such as the Black Death, which may have killed more than half of the entire population of Europe.
“Our data suggests that the insertion and then subsequent mutation of Pla allowed for new, rapidly evolving strains of disease,” says Wyndham Lathem, PhD, assistant professor in Microbiology-Immunology at Northwestern. “This information can show how new respiratory pathogens could emerge with only small genetic changes.”
“This research helps us better understand how bacteria can adapt to new host environments to cause disease by acquiring small bits of DNA,” Lathem concludes.
In May, Medical News Today reported that a small outbreak of pneumonic plague in Colorado was a result of the first incidence in the US of a human contracting the disease from a dog. The outbreak also marked the nation’s first case of human-to-human plague transmission in nearly a century.