By Briana Zellner

Ticks can be hosts to many different infectious diseases including Lyme disease and Rocky Mountain spotted fever. However, you may not be familiar with another important tick-borne disease called tularemia.

Tularemia, or rabbit fever, is caused by the bacterium Francisella tularensis (F. tularensis). F. tularensis can cause life-threatening infections that often are misdiagnosed as the flu.

If antibiotic treatment is not started early, tularemia can be fatal or can result in life-long health problems, including kidney and liver damage.

During the Great Depression era (1930s), there were over 10,000 cases of tularemia per year in the U.S., linked to either rabbit hunting or tick bites. Today, about 250 tularemia cases are reported each year in the U.S. Worldwide, there are thousands of tularemia cases each year. F. tularensis can be carried or cause disease in over 3,000 different animals.

Tularemia transmission

In addition to ticks, humans can become infected by eating or drinking contaminated food or water, being bitten by infected mosquitoes or flies, handling infected animal carcasses, or even inhaling air contaminated with the bacteria (mowing over an infected rabbit burrow/nest). These different infection routes can cause different disease symptoms, making tularemia extremely difficult to diagnose.

If quickly diagnosed, tularemia can be treated with antibiotics. However, there is no vaccine to prevent tularemia disease.

As a researcher in Dr. Jason Huntley’s lab at the University of Toledo College of Medicine and Life Sciences, I study how F. tularensis infects and causes disease. Using this information, our lab also works to develop new therapeutics and vaccines to prevent tularemia.

Every day we are exposed to millions of bacteria on our skin, in our lungs, and in our digestive tract. Luckily, we have specialized immune cells in our body that recognize invading bacteria, engulf, and kill them. These immune cells signal to other cells to alert them that the body is under attack so that infections can be quickly cleared.

Unfortunatley, F. tularensis is very good at avoiding these immune cells. In fact, F. tularensis actually can invade and replicate inside immune cells and many other cell types.

The bacteria have specialized proteins on their surface that allow them to invade and survive inside human cells. The bacteria also have a unique protective barrier, called the cell wall, which prevents them from being killed by our immune system.

The cell wall is a very important component of these bacteria. Think of it like a suit of armor or a bullet-proof vest designed to protect these bacterial invaders. If the armor is damaged or missing, the invaders are much more vulnerable to attack.

When immune cells encounter F. tularensis, they try to attack the bacteria and cause chinks in the armor. However, F. tularensis is very good at quickly repairing these chinks, infecting other cells, and reproducing to extremely high numbers – causing life-threatening disease.

Tularemia’s bacterial armor

Our lab has identified over 50 bacterial armor genes that allow F. tularensis to infect human cells and cause disease. Although these genes work together to protect the bacteria from our immune attack system, I have been able to use genetic tools to precisely delete only one armor gene to study.

I have found that these modified bacteria cannot replicate inside immune cells or cause disease in animals. When I examine these modified bacteria by electron microscopy, I have shown that they have abnormal cells walls – chinks in their armor.

Most importantly, I have recently shown that these modified bacteria can be used as a vaccine to protect animals from tularemia, similar to the modified chickenpox and measles, mumps, rubella (MMR) vaccines that are currently used.

Although I am a long way from testing this vaccine in humans, the potential to prevent human tularemia is exciting. In addition, because very little is known about the cell wall of F. tularensis, my project has provided new information about how we can develop new drugs to attack F. tularensis and potentially other bacteria.

Briana Zellner is a Ph.D. student in the Department of Medical Microbiology and Immunology in The University of Toledo College of Medicine and Life Sciences Biomedical Science Program. For more information, contact Briana.Zellner@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical. This article was originally published in The Toledo Blade. 

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