Source: https://lsuhscmicrobiology.com/kenneth-m-peterson-phd
Timestamp: 2019-04-22 20:05:09+00:00

Document:
Genetic and Biochemical Analysis of Bacterial Virulence Determinants, Coordinate Regulation of Virulence-Associated Genes, Chemotaxis, and Vaccine Development.
Virulence is a multifaceted property for enterotoxigenic Vibrio cholerae. For example, it is thought that V. cholerae utilizes motility and chemotaxis to penetrate the mucus gel overlaying the intestinal lining and cholera toxin to produce the secretory diarrhea associated with Asiatic cholera. These virulence properties or determinants are not expressed in a haphazard manner; they are carefully regulated in response to environmental signals. V. cholerae provides an excellent model system to study the coordinate regulation of microbial virulence properties. The orchestrated expression of three major virulence determinants [cholera toxin; a pilus colonization factor; and an accessory colonization factor] depends on a single regulatory protein designated ToxR. This protein senses environmental signals such as pH, osmolarity, and the presence of certain amino acids to control the selective expression of genes involved in cholera pathogenesis. My laboratory is using state of the art molecular biological, genetic and biochemical techniques to examine the mechanisms involved in the coordinate regulation of V. cholerae virulence determinants with the ultimate goal of developing efficacious cholera vaccines. The immediate goal of these experiments is to examine at a molecular level, the involvement of a set of four ToxR-regulated genes ( acf locus; a ccessory c olonization f actor) in the colonization properties of V. cholerae . Presently, we are attempting to biochemically characterize the ACF proteins so that we can understand their role in V. cholerae colonization of the small bowel. This information will be used to guide our genetic engineering experiments aimed at constructing stable V. cholerae mutants that may be useful for the development of a cholera vaccine.
We are also interested in understanding the role of methyl-accepting chemotaxis proteins in regulating the expression of the V. cholerae toxin coregulated pilus. Vibrios have adapted the sensory function of these chemotaxis proteins in order to express this major colonization determinant in response to microenvironmental factors within the small intestine. Molecular genetic approaches are being utilized to investigate the relationship between environmental signaling, intestinal colonization and vibrio pathogenesis.
Everiss, K. D., K. J. Hughes, M. E. Kovach, and K. M. Peterson. 1994. The Vibrio cholerae acf B colonization determinant encodes an inner membrane protein that is related to a family of signal transducing proteins . Infection and Immunity. 62:3289-3298.
Everiss, K. D., K. J. Hughes, and K. M. Peterson. 1994 . The accessory colonization factor and toxin-coregulated pilus gene clusters are physically linked on the Vibrio cholerae 0395 chromosome . DNA Sequence. 5:51-55.
Cassanova, T. B., and K. M. Peterson. 1995 . The Vibrio cholerae hlyC gene encodes a protein that is related to lipases of Pseudomonas species . DNA Sequence. 5:181-184.
Hughes, K. J., K. D. Everiss, M. E. Kovach, and K. M. Peterson. 1995. Isolation and characterization of the Vibrio cholerae aef A gene required for efficient intestinal colonization . Gene. 156:59-61.
Kovach, M. E., M. D. Shaffer, and K. M. Peterson. 1996. A putative integrase gene defines the distal end of a large cluster of ToxR-regulated colonization genes in Vibrio cholerae. Microbiology. 142:2165-2174.
K. M. Peterson. 1999. Molecular Pathogenesis of Vibrio infections. In: Microbial Foodborne Diseases. eds. J. W. Cary, J. E. Liuz & D. Bhatnager. Technomic Publishing Co. Lancaster, PA. pp. 157-190.
Selvaraj, P., Gupta, R., and K. M. Peterson. 2015. The Vibrio cholerae ToxR regulon encodes host-specific chemotaxis proteins that function in intestinal colonization. SOJ Microbiology and Infectious Diseases; 3:1-9.

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