NAU disease ecologist receives $2.25 million grant to study potential biological warfare agent

Dave Wagner

Francisella tularensis is one of the most infectious pathogenic bacteria known to science—so virulent, in fact, that it is considered a serious potential bioterrorist threat. Humans can contract respiratory tularemia—a rare and deadly disease—by inhaling as few as 10 airborne organisms.

Northern Arizona University professor David Wagner, director of the Pathogen and Microbiome Institute’s (PMI) Biodefense and Disease Ecology Center, was recently awarded a $2.25 million grant by the U.S. Defense Threat Reduction Agency (DTRA) for a three-year project to better understand the life cycle and behavior of F. tularensis.

Wagner, who has been performing advanced DNA “fingerprinting” of this pathogen for almost 15 years, said that because some countries have developed biological warfare agents based on F. tularensis, it is imperative that the U.S. government develop the tools and knowledge to protect Americans from this potential threat.

“This project is critical to the science of countering weapons of mass destruction because F. tularensis is a potential biological warfare agent and its natural life cycle is poorly understood,” Wagner said.

Pathogen’s dormant state puzzles scientists

One of the most enigmatic behaviors of the pathogen is its ability to remain dormant, in what is called a “viable but nonculturable” state—which means the bacteria is alive, but cannot be grown in the laboratory. That makes it much more difficult to study, because scientists can typically only study bacteria that can be cultured.

By performing whole-genome sequencing studies, which examine the organism’s entire genome, Wagner’s team found strains that were nearly identical genetically but separated by up to hundreds of miles and 10 years apart.

“Usually, a bacteria species will get inside a host, such as an insect or rodent, and multiply. We’d expect to see natural genetic mutations as a result,” Wagner said. “But because these strains had not mutated as we would have expected if they’d been inside a host, we theorized that the organisms were persisting in the environment in this dormant state.”

Working with co-principal investigator Jason Sahl, assistant professor and assistant director of PMI, and with long-term collaborators at the Swedish Defence Research Agency and Umeå University, Wagner hopes to determine the environmental and genetic factors that contribute to the pathogen’s ability to remain dormant in the environment.

Although the bacteria are naturally occurring throughout the northern hemisphere, including Arizona, the number of reported cases in the United States is small, with only 230 cases in 2016, three of which occurred in Arizona. Humans can be infected through insect bites; by drinking contaminated water, which happens in developing countries such as Turkey; by handling infected animals; and by breathing aerosolized particles containing the bacteria. Humans cannot transmit the disease to other humans.

There is no vaccine to prevent tularemia, also known as rabbit fever. The disease is treated with antibiotics, and Wagner’s team is working on a related project funded by the DTRA studying the pathogen’s antibiotic resistance.

Team known worldwide for developing phylogeny and phylogeography of the species

Along with their Swedish collaborators, Wagner and his team are known worldwide for their work developing the phylogeny, or global family tree, of F. tularensis and its phylogeography—mapping where different groups of the species are found throughout the world and understanding the species’ genetic diversity.

“We are excited to get this project started,” Wagner said. “We have an excellent team of scientists here at NAU and with our Swedish collaborators.”

Both undergraduate and graduate students will be working in Wagner’s lab on this project, generating data from DNA and RNA samples.

Wagner is a disease ecologist whose primary research interests are the ecology and evolution of infectious diseases. He uses genetic and genomic variation within pathogen, vector and host species to better understand the distribution, ecology, evolutionary history and trans­mission patterns of infectious diseases. Wagner, who has published more than 100 articles in scholarly journals, is one of the world’s leading experts on several pathogens and infectious diseases, including plague and tularemia. Other recent grants include two from the Centers for Disease Control and Prevention totaling $454,000 to study the prevalence of Burkholderia pseudomallei, an infectious pathogen that causes melioidosis, in Puerto Rico and the U.S. Virgin Islands.

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