Black death: Scanning electron micrograph depicting a mass of Yersinia pestis in the foregut of a flea vector.

Credit: Rocky Mountain Laboratories, NIAID, NIH

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SYDNEY: Bacteria responsible for bubonic plague are more virulent than their close relatives because of a single genetic mutation, says a new study. The discovery may lead to treatments for a group of diseases that strike in the same way.

Carried by fleas, bubonic plague has killed over 200 million people during the course of history. It is the most devastating acute infectious diseases known to man.

Despite this, experts have still been uncertain about the molecular basis of its extraordinary ability to spread and kill.

Single mutation

Researchers did know that it recently diverged from a related, but typically harmless, bacterium. This suggested that small changes were responsible for the pathogen's vigour.

To learn more, microbiologists led by Robert Brubaker of the University of Chicago in Illinois, U.S., analysed the plague bacterium's genes and then experimentally swapped chunks of its DNA with it's less virulent relative.

They report their results this month in the journal Microbiology.

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

"The plague bacterium … 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," he said. "We found that this is because Y. pestis is missing an important enzyme."

The enzyme aspartase is present in almost all bacteria but it is curiously absent in many pathogenic types. These include mycobacteria that are pathogenic to man and also spread via insects such as Francisella tularensis (which causes tullaremia or rabbit fever) and Rickettsia (responsible for a variety of tick-borne diseases).

Treatment clues

Though the researchers are not sure of the mechanism, "this suggests that the absence of aspartase may contribute to serious disease," said Brubaker.

One idea is that the aspartic acid increases the acidity of cells in people or animals struck down by plague, potentially making more calcium available – but also wreaking havoc within the host.

"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 Brubaker.