High-throughput sequencing was used to detect changes in sRNA that may account for plague’s virulence.

Using high-throughput DNA sequencing, researchers at Northwestern University Feinberg School of Medicine have found that changes in small, non-coding RNAs (sRNAs) account for the rapid evolution of Yersinia pseudotuberculosis into the deadly plague, or Yersinia pestis.

In findings published Aug. 29 in the journal Proceedings of the National Academy of Sciences, the team concluded that sRNAs in Yersinia affect virulence. While the former causes a mild gastrointestinal disease, and many people don’t show symptoms, the latter can evolve from an infection to death in up to five days.

Wyndham Lathem, lead author of the study and assistant professor of microbiology-immunology at Feinberg, led the research team in using high-throughput sequencing to identify the complete set of sRNAs produced by Y. pseudotuberculosis. Unlike messenger RNA, the sRNAs never translate into proteins.

“Once we identified the complete set of sRNAs for Y. pseudotuberculosis, further analysis unlocked a number of surprising discoveries about their function,” Lathem said.

Lathem’s team identified 150 sRNAs, most of which are specific to Yersinia, as well as six sRNAs unique to Y. pseudotuberculosis. The six sRNAs are missing in Y. pestis, believed to have been lost during its rapid evolution, and thereby potentially responsible for the plague’s virulence.

The plague accounts for 1,000 to 3,000 cases annually, according to the World Health Organization, and is classified by the U.S. Department of Homeland Security as a category A biological agent, as are anthrax, smallpox, and Ebola.

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