Biochemical mechanisms of protein toxin action and their contribution to progression of bacterial infection

Friday, September 28, 2012

3:00 p.m.   Morken 103

Refreshments and conversation at 2:40

Professor Karla Satchell (PLU '88)
Associate Professor of Microbiology-Immunology
Feinberg School of Medicine
Northwestern University

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Summary:  Bacterial - host interactions frequently involve mechanisms for translocation of “effector” proteins from bacteria into eukaryotic cells. Within the host cell, these effectors modulate cell biological processes resulting in cytopathic and sometime cytotoxic effects that ultimately benefit the infectious agent.  The Satchell lab studies toxins that deliver numerous effectors to cells; these are known as the Multifunctional-Autoprocessing RTX (MARTX) toxins. The toxins themselves are very large single polypeptides (ranging from 3500-5200 aa) that are secreted from bacteria. The central portion of the toxins are subsequently transferred into eukaryotic cells where the toxin is activated by binding a small molecule that initiates the toxin to process itself. The released protein fragments are effectors that are then free in the cytosol to access cellular targets to initiate cytopathic and cytotoxic effects. A notable feature distinguishing MARTX toxins of different species is that the effector repertoire can vary with a single toxin carrying anywhere from 1 to 5 effectors.  Dr. Satchell will present data demonstrating how autoprocessing leads to delivery of effectors and how distinct toxins with different effector combinations can lead to dramatically different disease outcomes after intestinal infection, from diarrhea to septicemia and necrotizing fasciitis.

Biography:  Dr. Karla Satchell (nee Fullner) graduated from PLU with a B.S. in Biology and minor in Chemistry in 1988.  After graduating, she worked as a technician at the University of Washington Department of Pharmacology for 2 years gaining valuable research experience and starting what would become a life long interest in bacterial toxins.  She entered the graduate program in Microbiology at the University of Washington and completed a Ph.D. studying how the bacterium Agrobacterium tumefaciens transfers DNA to plant cells.  Her graduate work was published in the journal Science.  She then studied at the University of Pittsburgh examining bacteriophages of Mycobacterium and how these phages infect the bacterium responsible for tuberculosis.  In 1997, she moved to Harvard Medical School in Boston to conduct research on the bacterium Vibrio cholerae.  As part of this work, she returned to her original interest in bacterial toxins, ultimately discovering and characterizing a new family of toxins known as the MARTX toxins. She joined the faculty at Northwestern University Feinberg School of Medicine in Chicago in 2000 and has built a vigorous research program focused on toxins and how these toxins contribute to progression of bacterial infections.  Her work centers on two bacteria: Vibrio cholerae and how toxins contribute to cholera disease and Vibrio vulnificus, a seafood-bourne pathogen that causes severe septicemia and necrotizing fasciitis. Dr. Satchell’s research is highly interdisciplinary crossing the fields of microbiology, immunology, cell biology, biochemistry, and structural biology.  Her current research group has eight scientists and funding from the National Institutes of Health and private foundations.   She has published nearly 50 research articles. In addition, Dr. Satchell is the proud mother of 7 year old son Grant and serves as a consultant to Situ Biosciences, a start-up biotech company founded by her husband.