Research Interests: Bacterial toxins are multifunctional proteins designed by bacteria to manipulate the eukaryotic cell environment with which they co-exist. Toxins frequently include a common enzymatic activity and manipulate eukaryotic cells by altering the function of proteins integral to cellular processes. Studies in our laboratory explore the design and function of a large family of toxins that include an ADP-ribosyltransferase enzyme activity. Within eukaryotic cells, bacterial toxins target and affect the function of proteins integral to signal transduction. One toxin studied, ExoS, is directly translocated into eukaryotic cells by the bacterial type III secretory process, and provides the bacterium with a mechanism for directly manipulating eukaryotic cells it contacts. Using ExoS and other bacterial toxins, studies in our laboratory are directed at examining: 1) the role of bacterial toxins in infectious disease; 2) how bacteria use toxins to manipulate eukaryotic cell function; 3) the use bacterial toxins as tools to understand complex mechanisms of signal transduction in normal and abnormal cells; and 3) the use of bacterial toxins as specific therapeutic agents. Recent publications derived from these studies include:
Funding: National
Institutes of Health, National Institute of Allergy and Infectious Diseases
Department of Defense (DOD) Hollings Cancer Center Core Development Grant
Recent Publications:
Vincent, T.S., J.E. Fraylick, E.M. McGuffie, J.C. Olson. 1998. ADP-ribosylation of oncogenic Ras proteins by Pseudomonas aeruginosa exoenzyme S in vivo. Mol. Microbiol. 32:1054-1064, 1999.
Olson, J.C., J.E. Fraylick, E.M. McGuffie, K.M. Dolan, T.L. Yahr, D.W. Frank, T.S. Vincent. Interruption of multiple cellular processes in HT-29 epithelial cells by Pseudomonas aeruginosa Exoenzyme S. Infect. Immun. 67:2847-2854, 1999.
McGuffie, E.M., J.E. Fraylick, D.J. Hazen-Martin, T.S. Vincent, J.C. Olson. Differential sensitivity of human epithelial cells to Pseudomonas aeruginosa exoenzyme S. Infect. Immun. 67:3494-3503, 1999.
Ganesan, A.K., T.S. Vincent, J.C. Olson, J.T. Barbieri. Pseudomonas aeruginosa exoenzyme S disrupts Ras-mediated signal tranduction by inhibiting guanine nucleotide exchange factor catalyzed nucleotide exchange. J. Biol. Chem. 274:21823-21829, 1999.
Dolan, K.M., G. Lindenmayer, J.C. Olson. Functional comparison of the NAD-binding cleft of ADP-ribosylating toxins. Biochemistry 39:8266-8275, 2000.
Ferguson, M.W., #J.A. Maxwell, T.S. Vincent, J. de Silva, J.C. Olson. Comparison of the exoS gene and protein expression in soil and clinical isolates of Pseudomonas aeruginosa. Infect. Immun. 69:2198-2210, 2001.
Fraylick, J. E., J.R La
Rocque, T.S. Vincent, J.C. Olson. Independent and coordinate effects of the
ADP-ribosyltransferase and GTP-ase activating activities of exoenzyme S on HT-29
epitheilial cell function. Infect. Immun. 69:5318-5328, 2001.
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