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Faculty

Maria Sandkvist

Assistant Professor
Ph.D, Umea University, 1992
mariasan@umich.edu




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Bacterial pathogenesis: Molecular mechanism of extracellular protein secretion

Extracellular secretion of proteins is one of the primary virulence mechanisms in bacterial infection. Gram-negative bacteria pathogenic for humans, animals and plants secrete a number of proteins that are responsible for causing disease. Several different secretion pathways have evolved for this purpose. The type II secretion (T2S) pathway appears to be the most widely distributed pathway and has been identified in pathogens such as Vibrio cholerae, Escherichia coli O157, Pseudomonas aeruginosa, Legionella pneumophila and Yersinia enterocolitica where it is responsible for secretion of toxins and hydrolytic enzymes including proteases and lipases.

The aims of our studies are to 1) determine the mechanism of T2S and to 2) characterize the T2S apparatus so that we may identify novel ways to manipulate the secretion process for preventative, therapeutic and biotechnological use. As a model system we use Vibrio cholerae, the causative agent of cholera, which is a life-threatening diarrheal disease endemic to many developing countries. V. cholerae secretes cholera toxin via the T2S pathway and this toxin is in large part responsible for the symptoms of cholera. Our studies investigate and map specific protein-protein interactions that are involved in the assembly of the T2S complex Eps in V. cholerae, which is composed of at least 13 different proteins. In addition, we have recently determined that the Eps complex is predominantly localized to one of the cell poles of V. cholerae, where secretion occurs. Studies are in progress to 3) determine the mechanism of polar localization of the Eps system and to 4) investigate the importance of polar secretion and targeted delivery of virulence factors in V. cholerae infection.

Selected Publications:

Abendroth, J., Murphy, P., Sandkvist, M., Bagdasarian, M., and Hol, W.G.J. The X-ray structure of the type II secretion pathway complex formed by the N-terminal domain of EpsE and the cytopasmic domain of EpsL of Vibrio cholerae. Journal of Molecular Biology, 348:845-855, 2005.

Camberg, J. and Sandkvist, M. Molecular analysis of the Vibrio cholerae type II secretion ATPase EpsE. Journal of Bacteriology, 187:249-256, 2005.

Abendroth, J., Bagdasarian, M., Sandkvist, M., and Hol, W.G.J. The structure of the cytoplasmic domain of EpsL, an inner membrane component of the type II secretion system of Vibrio cholerae: an unusual member of the actin-like ATPase superfamily. Journal of Molecular Biology, 344:619-633, 2004.

Robien, M.A., Krumm, B.E., Sandkvist, M., and Hol, W.G.J. Crystal structure of the extracellular protein secretion NTPase EpsE of Vibrio cholerae. Journal of Molecular Biology, 333:657-674, 2003.

Scott, M.E., Dossani, Z.Y., and Sandkvist, M. Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway. Proc. Natl. Acad. Sci. USA. 98:13978-13983, 2001.

Sandkvist, M. Biology of type II secretion. Review. Molecular Microbiology 40:271-283, 2001.