The bubonic plague, caused by the bacterium Yersinia pestis, is infamous for causing the Black Death that wiped out millions of people in the mid-fourteenth century. However, a recent study published in Science reveals that a small genetic tweak in this deadly bacterium has made it less fatal but potentially more transmissible.
Researchers found that reducing the copies of a gene called pla in Y. pestis resulted in a less severe form of the disease. This genetic change may have allowed the bacterium to spread more easily in smaller populations. The study’s co-author, Ravneet Sidhu, a palaeogeneticist at McMaster University, describes this as a case where a pandemic-causing pathogen has evolved to become slightly weaker.
To investigate the impact of this genetic modification, the research team infected mice with different strains of Y. pestis. Mice infected with the strain with reduced levels of pla lived longer and had a lower mortality rate compared to those infected with the normal strain. However, when the bacteria were introduced through different routes, such as intravenously or through the nose, the reduced pla strain was as deadly as the normal strain.
Analysis of ancient and modern strains of Y. pestis revealed that between 30% and 50% of these strains showed signs of pla depletion. The researchers identified a specific region in the genome where a 2,100-base-pair-long segment containing the pla gene had been deleted. This deletion, along with the integration of a DNA molecule called a plasmid, led to the reduction of pla in certain strains.
Francesca Short, a microbiologist at Monash University, emphasizes the significance of these findings, highlighting how small genetic changes can have a substantial impact on pathogen transmission. She notes that even minor alterations like the dosage change in pla can affect virulence and transmission potential.
While the study sheds light on the evolution of Y. pestis and its implications for disease spread, Sidhu cautions against extrapolating these findings to other pathogens like SARS-CoV-2. Each pathogen has its unique characteristics, and further research is necessary to understand how different diseases evolve and behave.
This study underscores the complex interplay between genetics, virulence, and transmission in infectious diseases. By unraveling the genetic mechanisms that shape the evolution of pathogens like Y. pestis, researchers can gain insights into how these microorganisms adapt and survive in changing environments.
