Attenuation of virulence in Yersinia pestis across three plague pandemics

Scientists have documented the way a single gene in the bacterium that causes bubonic plague, Yersinia pestis, allowed it to survive hundreds of years by adjusting its virulence and the length of time it took to kill its victims, but these forms of plague ultimately died out. A study by researchers at McMaster University and France's Institut Pasteur, published today in the journal Science, addresses some fundamental questions related to pandemics: how do they enter human populations, cause immense sickness, and evolve different levels of virulence to persist in populations? Using hundreds of samples from ancient and modern plague victims, the team screened for a gene known as pla, a high copy component of Y. pestis which helps it move through the immune system undetected to the lymph nodes before spreading to the rest of the body. An extensive genetic analysis revealed that its copy number had decreased in later outbreaks of the disease, which in turn decreased its mortality by 20 per cent and increased the length of its infection (studies performed in mouse models). Conversely, when the pla gene was in its original, high copy number, the disease was much more virulent and killed hosts much faster. The researchers observed similar independent reductions in pla across the first and second pandemics (and in three contemporary samples from the third pandemic, found in Vietnam), suggesting a repeated evolutionary trajectory where pla copy-number reduction led to longer host survival and enhanced pathogen persistence, but these pla-reduced strains eventually went extinct.