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Associate Professor
Contact Information:
Email: dshelv@lsuhsc.edu
Office Phone: 318-675-4884
Laboratory Phone: 318-675-5111
Office Fax: 318-675-5764
Education/Training:
Postdoctoral Study, University of Washington/Seattle Children's Hospital
Ph.D., 1998, Bacteriology, University of Wisconsin-Madison
B.S., 1991, Biochemistry, University of Minnesota-Twin Cities
Major Research Interests: Mechanisms of Pathogenesis of Group B Streptococcus.
Group B Streptococcus (GBS) is a significant pathogen of neonates and of select adult populations. In neonates, GBS can cause pneumonia, meningitis, and sepsis. However, relatively few virulence factors have been characterized for this pathogen. We are interested in the discovery and characterization of GBS virulence factors in order to understand how this bacterium causes disease. To accomplish this, we use targeted gene knockout, in vitro and in vivo models of pathogenesis, transcriptional profiling and proteomics, and protein purification and characterization. One of the properties that contributes to GBS virulence is its ability to evade the innate immune system during an infection. We are characterizing an extracellular protease, CspA, which promotes virulence and resistance to the innate immune system. This protease belongs to a family of proteases that localize to the cell envelope. It exhibits a degree of specificity in that it has the ability to cleave chemokines, fibrinogen, and other molecules involved in host defense, but does not cleave other most molecules. We are currently investigating the role of this protease in pathogenesis. A second research interest is the regulation of GBS virulence. During the infection process, GBS encounters a variety of different host environments and must adapt to these different conditions. It is our hypothesis that the transcriptional regulatory proteins encoded on the genome of GBS control its ability to transition between different host environments. The analysis of GBS strains that harbor mutations in genes encoding these transcriptional regulatory proteins and the targets of their regulation will give insight into how GBS adapts to host environment and how virulence factors are regulated.
Representative Publications:
Shelver D., Thorsteinsson, M.V., Kerby, R.L., Chung, S.Y, Roberts, G.P, Reynolds, M.F., Parks, R.B., and Burstyn, J.N. 1999. Identification of two important heme site residues (cysteine 75 and histidine 77) in CooA, the CO-sensing transcription factor of Rhodospirillum rubrum. Biochemistry 38: 2669-2678.
Harris, T.O.*, Shelver, D. W.*, Bohnsack J.F., and Rubens, C.E. 2003. A novel streptococcal protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen. J. Clin. Invest. 111: 61-70 *denotes authors contributed equally to this work.
Shelver, D.W., Rajagopal, L., Harris, T.O., and Rubens, C.E. 2003. MtaR, a regulator of methionine transport, is critical for survival of Group B Streptococcus in vivo. J. Bacteriol. 185:6592-6599.
Shelver, D., and Bryan, J. D. 2008. Expression of the Streptococcus agalactiae virulence-associated protease CspA in a soluble, active form utilizing the Gram-positive host, Lactococcus lactis. J. Biotechnol. 136: 129-134.
Bryan, J. D., Liles, R., Cvek, U., Trutschl, M., and Shelver, D. 2008. Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor. BMC Genomics 9:607.
Bryan, J. D., and Shelver, D. 2009. Streptococcus agalactiae CspA is a serine protease that inactivates chemokines. J. Bacteriol. 191: 1847-1854.
Quanch, D., van Sorge, N. M., Kristian, S. A., Bryan, J. D., Shelver, D. W., and Doran, K. S. 2009. The CiaR Response regulator in group B Streptococcus promotes intracellular survival and resistance to innate immune defenses. J. Bacteriol. 191: 2023-2032.
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