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Biographical
Sketch
Dr. Karla J. Fullner Satchell earned her bachelor’s degree in biology at Pacific Lutheran University in 1988 and her PhD in microbiology from the University of Washington, Seattle, in 1996. Karla did post-doctoral research in microbial
pathogenesis in the laboratories of Graham Hatfull at University of Pittsburgh and John Mekalanos at Harvard Medical School. She joined the department as an assistant professor in 2000.
Contact Information:
Office location: Tarry 3-713
Office: (312) 503-2162
Lab: (312) 503-1503
e-mail: k-satchell@northwestern.edu
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Research
Description
Molecular pathogenesis of Vibrio cholerae; structure/function studies of the Vibrio RTX toxin; host-pathogen interactions in animal and cell culture systems.
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Research
Abstract
The disease Asiatic cholera occurs worldwide with over 250,000 cases reported to the World Health Organization in 1999. However, due to inaccurate reporting by many affected countries, it is estimated that the actual
incidence of disease is between 5 and 7 million per year with over 100,000 deaths. This diarrheal disease is caused by the Gram-negative bacterium Vibrio cholerae found in estuarine environments throughout the world. Upon ingestion
of contaminated water or food by a person, V. cholerae colonizes the mucosa of the upper intestine and begins to export enterotoxins, including the major virulence toxin, cholera toxin (CT). The activity of CT elicits severe diarrhea in the infected host resulting in
extreme dehydration.
However, CT is not the sole toxin exported by V. cholerae. In human volunteer studies it has been shown that CT-deficient strains still elicit mild to severe diarrhea, vomiting, and other symptoms of discomfort. The search for the "reactogenicity
factor" has been an ongoing process in many laboratories and has led to the discovery of numerous exported proteases and a hemolysin. My lab focuses primarily on a newly discovered toxin, the RTX toxin.
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The RTX toxin of V. cholerae causes rounding of cells in culture. This rounded occurs because the actin cytoskeleton is depolymerized. As shown in the figure, the actin stress fibers (green) are disorganized when
cells are exposed to V. cholerae but not a strain that doesn’t produce the RTX toxin. However, unlike any other known toxin, this depolymerization apparently results from covalent crosslinking of the cellular actin molecules! Western blot analysis of cell extracts using
anti-actin antibody shows that virtually all of the actin molecules in RTX toxin exposed HEp-2 cells is absent and replaced by dimers, trimers, and other higher order oligomers of actin.
Projects within my lab include structure/function analysis of the toxin, cell biological and biochemical studies to elucidate the mechanism of covalent crosslinking of actin, and association of the RTX toxin with pathogenesis in
animal and relevant culture models.
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Publications
Boardman BK, Satchell KJ. Vibrio cholerae strains with mutations in an atypical type I secretion system accumulate RTX toxin intracellularly.<>
J Bacteriol. (2004) 186:8137-43.
Sheahan KL, Cordero CL, Satchell KJ. Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin. Proc Natl Acad Sci U S A. (2004)
101:9798-803.
Satchell KJ. Activation and suppression of the proinflammatory immune response by Vibrio cholerae toxins. Microbes
Infect. (2003) 5:1241-7.
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