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Uncovering the Secrets of Tularemia, the "Rabbit Fever"

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The functions of novel proteins putatively involved in F. tularensis virulence are revealed by X-ray crystallography. Image: LLNL/G. K. Feld/CDC

The functions of novel proteins putatively involved in F. tularensis virulence are revealed by X-ray crystallography. Image: LLNL/G. K. Feld/CDC

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Washington, DC (Scicasts) – Tularemia, aka "rabbit fever," is endemic in the northeastern United States, and is considered to be a significant risk to biosecurity -- much like anthrax or smallpox -- because it has already been weaponized in various regions of the world.

At the 58th Annual Biophysical Society Meeting, which takes place Feb. 15-19, 2014, in San Francisco, Calif., Geoffrey K. Feld, a Postdoctoral researcher in the Physical & Life Sciences Directorate at Lawrence Livermore National Laboratory (LLNL), describes his work to uncover the secrets of the bacterium Francisella tularensis, which causes tularemia.

"Despite its importance for both public health and biodefense, F. tularensis pathogenesis isn't entirely understood, nor do we fully understand how the organism persists in the environment," explained Feld.

Previous efforts, funded by both the National Institutes of Health and LLNL, demonstrated that amoebae may serve as a potential reservoir for the bacteria in nature. "Specifically, we demonstrated that amoebae exposed to fully virulent F. tularensis rapidly form cysts -- dormant, metabolically inactive cells -- that allow the amoebae to survive unfavourable conditions," said Amy Rasley, the research team leader.

This encystment phenotype was rapidly induced by F. tularensis in the laboratory and was required for the long-term survival of the bacteria. Further exploration led to the identification of secreted F. tularensis proteins, which are responsible for induction of the rapid encystment phenotype (REP) observed in amoebae.

In the new work, Feld and colleagues characterized two of these REP proteins -- called REP24 and REP34 -- and began to describe their functions based on their three-dimensional crystal structures.

A big surprise finding was that these proteins resembled "proteases," which are proteins that cut other proteins in a specific manner. "Our preliminary data indicate that F. tularensis bacteria lacking these proteins are diminished in their ability to infect or survive in human immune cells, which indicates that these proteins may also contribute to F. tularensis virulence," Feld said.

Rasley and colleagues believe that careful characterization of these two novel F. tularensis proteins may shed light on how this organism persists in the environment and causes disease.

"Ultimately, this type of research could inform efforts to combat the disease, although there is much work to do. Currently, we don't know the protein targets in the host -- amoeba, human, etc. -- that the REP proteins act on, nor do we know the mechanism by which the proteins could help F. tularensis survive in the environment or cause disease," Feld said.

"Once these questions are elucidated, a broader understanding of environmental persistence and pathogenesis might lead to better diagnostics and/or novel countermeasures to combat tularemia," he added.

Presentation Abstract: Structure and Function of Two Putative Virulence Factors from Francisella tularensis. Geoffrey K. Feld. Biophysical Society (2014): http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=00f85393-c521-47ca-9ba4-03feb96058ce&cKey=eb3c369b-6ee6-4259-86a8-fa15dba5920c&mKey=65c07790-3dc0-4a68-a0f7-e533a63e290d

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