New research into tularemia or “rabbit fever” yields a more sophisticated picture of the disease that scientists say pose a significant risk to biosecurity.

Dr. Geoffrey K. Feld, postdoctoral fellow at the Lawrence Livermore National Laboratory, said in a press release that the findings may broaden the current understanding of  F. tularensis, the bacterium that causes tularemia —an infectious disease often transmitted via rabbits, hares, and rodents. "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,” he said.

The new study, which was presented at the 58th Annual Biophysical Society Meeting in San Francisco, shows among other things that the bacterium uses amoebae to survive in outside human or animal hosts.  "Specifically, we demonstrated that amoebae exposed to fully virulent F. tularensis rapidly form cysts — dormant, metabolically inactive cells — that allow the amoebae to survive unfavorable conditions," said lead author Amy Rasley.  

This so-called rapid encystment phenotype (REP) was subsequently shown to be driven by a specific group of proteins. Two of these proteins, referred to as REP24 and REP 34 in the study, appear to determine the pathogen’s ability to infect humans. "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 explained.

What is Tularemia?

The Centers for Disease Control and Prevention describes tularemia as a highly infectious disease that can enter the human body through the skin, eyes, mouth, throat, or lungs. Although the symptoms differ depending on the pathogen’s point of entry, the most common signs include ulcers, fever, and swelling of the lymph glands. Pneumonic tularemia, the most dangerous form of the disease, is also characterized by chest pain and difficulty breathing. Although the treatment course typically lasts for several weeks, most patients completely recover.

While tularemia is a household threat among hikers, the pathogen is perhaps better known as one of the first examples of biological warfare. Ancient Middle Eastern documents dating back over 3,000 years describe how the Hittites, an Anatolian people whose empire covered much of modern-day Turkey and Syria, would release hordes of “cursed” rams into the battle field to weaken the enemy.  Without antibiotics, tularemia kills about 15 percent of the people it infects, New Scientist explains.

Although it is not yet clear precisely how these discoveries will inform better treatment and prevention strategies against the disease, Rasley and her colleagues are confident their findings warrant further inquiry. “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 told reporters. "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.”

Source: Rasley A, Feld GK, et al. Structure and Function off Two Putative Virulence Factors From Francisella Tularensis. Presented at the “58th Annual Biophysical Society Meeting.” 2014.