Recent Mutations Responsible for Plague Bacteria's Virulence

A team of molecular microbiologists has found that acquisition of single protein early in its existence enabled the plague bacterium Yersinia pestis to invade lung tissue, but that it required later mutations of this gene to enable the organism to rapidly spread to the lymph nodes and cause the bubonic form of the disease.

Yersinia pestis, a Gram-negative bacterium that causes bubonic and pneumonic plague, is able to rapidly disseminate to other parts of its mammalian hosts. Y. pestis expresses the enzyme plasminogen activator (Pla) on its surface, which has been suggested to play a role in bacterial dissemination.

Investigators at Northwestern University (Evanston, IL, USA) worked with ancestral strains of Y. pestis in mouse models. They found that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. However, at this stage the bacterium did not cause the fulminating form of pneumatic plague, nor could it disseminate to the lymph nodes to cause the bubonic form.

It became apparent that as Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimized protease activity. While this modification was unnecessary to cause pneumonic plague, the substitution was instead needed to efficiently induce the invasive infection associated with bubonic plague.

"Our findings demonstrate how Y. pestis had the ability to cause a severe respiratory disease very early in its evolution," said senior author Dr. Wyndham Lathem, assistant professor of microbiology and immunology at Northwestern University. "This research helps us better understand how bacteria can adapt to new host environments to cause disease by acquiring small bits of DNA. Our data suggests that the insertion and then subsequent mutation of Pla allowed for new, rapidly evolving strains of disease. This information can show how new respiratory pathogens could emerge with only small genetic changes."

The study was published in the June 30, 2015, online edition of the journal Nature Communications.

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