SBRI - Research: Scientists

Mission
The research underway in the Freitag lab is focused on understanding how pathogens make themselves at home within human cells, and to discover how cells might fight off pathogenic intruders.

Research
Intracellular pathogens are responsible for devastating amounts of morbidity and mortality worldwide. The list of intracellular infectious agents that have had a significant impact on global health and economy includes viral pathogens (responsible for AIDS, hepatitis, influenza), protozoan parasites (causative agents of Chagas disease, malaria, leishmaniasis), and bacterial pathogens (including the agents responsible for tuberculosis, chlamydia, leprosy). The understanding of the molecular and cellular basis of intracellular pathogenesis is limited, and this lack of knowledge in many instances has severely reduced the ability to develop effective means of combating or preventing infection.

Dr. Freitag and scientists in her laboratory have chosen to study Listeria monocytogenes because it is an important agent of food-borne infections and because it serves as a very useful model system for exploring the intracellular interactions that take place between pathogen and host. L. monocytogenes represents an increasingly significant health threat as it has been associated with several multi-state food-borne outbreaks that have resulted in thousands of illnesses and several hundred deaths within the past few years. L. monocytogenes is a particularly challenging pathogen with regards to food safety, as it is capable of growth under conditions normally designed to limit bacterial replication in food products. Infections caused by L. monocytogenes pose serious risks to growing populations of immunocompromised patients and the elderly, as well as to pregnant women and neonates.

SBRI is working to define the mechanisms used by L. monocytogenes to survive within human cells to determine if similar strategies are used by other deadly parasites. This information will help foster the development of new drug targets and antimicrobials designed to combat infectious disease.

Themes
     * Regulation of bacterial virulence gene expression within host cells
     * Host responses to bacterial infection
     * Pathogen survival within host cells

Accomplishments
*	Identified key regulatory switches used by the bacteria to makes themselves at home within human cells. These switches must be engaged at the proper time to promote bacterial infection.
*	Isolated bacterial mutants that ‘think’ they are inside of host cells. These mutants produce proteins in broth culture that are normally only made within infected cells. We are beginning to identify these proteins and discover their functional roles in disease.
*	Developed a new host system that will allow us to explore early host defenses to Listeria infection. Surprisingly, the common fruit fly fights off bacterial infection using many of the same defenses as human cells. We can explore and identify defensive strategies in the fly and then look for their counterparts in humans.

These accomplishments will be useful for:
*	Improved diagnostics. L. monocytogenes looks very different when it’s inside vs. outside of host cells. Improved food detection strategies must be designed to recognize intracellular and extracellular bacteria.
*	Improved therapies. Significant mortality occurs in patients with listeriosis even with antibiotic therapy. By defining the spectrum of host defenses used to fight bacterial infection, we may be able to develop ways of improving those defenses and strengthening the host attack.
*	Insights into host survival strategies for other pathogens.

Collaborations
     * University of Washington Medical Center
     * Stanford University
     * Veterans Affairs Medical Center, Portland OR
     * Harvard University
     * Cornell University
     * German Research Centre for Biotechnology, Germany

Dr. Freitag’s research is currently supported by the National Institutes of Health (NIH) and the Puget Sound Partners for Global Health.