Scientists discover why plague is so lethal

May 19 2008

Bacteria that cause the bubonic plague may be more virulent than their close relatives because of a single genetic mutation, according to research published in the May issue of the journal Microbiology.

"The plague bacterium Yersinia pestis needs calcium in order to grow at body temperature. When there is no calcium available, it produces a large amount of an amino acid called aspartic acid," said Professor Brubaker from the University of Chicago, USA. "We found that this is because Y. pestis is missing an important enzyme."

Bubonic plague has killed over 200 million people during the course of history and is thus the most devastating acute infectious disease known to man. Despite this, we are still uncertain about the molecular basis of its extraordinary virulence.

"Y. pestis evolved from its ancestor Y. pseudotuberculosis within the last 20,000 years, suggesting its high lethality reflects only a few genetic changes. We discovered that a single mutation in the genome of Y. pestis means the enzyme aspartase is not produced," said Professor Brubaker.

Aspartase is present in almost all bacteria but it is curiously absent in many pathogenic types. These include mycobacteria that are pathogenic to man, Francisella tularensis and rickettsiae (both of which cause diseases transmitted to humans via insects). "This suggests that the absence of aspartase may contribute to serious disease," said Professor Brubaker.

Aspartase digests aspartic acid. Because Y. pestis doesn't have the enzyme, it produces much more aspartic acid than is required by the person infected. This may cause an imbalance to the host amino acid pools. "If this is the case then we might be able to reduce the death rates of these diseases by developing a treatment that removes some of the extra aspartic acid," said Professor Brubaker.