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Characterization of Shiga Toxin Potency and Assembly

Pellino, Christine A.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1418909563

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
   Shiga toxin (Stx) producing Escherichia coli (STEC) are a major cause of foodborne illness. Complications including kidney failure and neurological symptoms can be fatal. Currently, supportive care is the only treatment. Stx is considered an AB5 toxin; the single, enzymatically active A-subunit and homo-pentameric, binding B-subunit are both essential for toxicity. Encoded on a bacteriophage, Stx is released by virus-mediated cell lysis. Since secretion systems can act as quality control mechanisms to ensure release of assembled toxin, we investigated whether phage-mediated lysis results in significant release of unassembled A- and B-subunits. We show here that little assembled toxin is released by bacterial lysis and that pre-formed AB5 complex is not required for cellular toxicity or in vivo toxicity to mice.    There are two major antigenic forms of Stx, Stx1 and Stx2 with minor variants of Stx2 (Stx2 a to h). While they share a significant amount of amino acid identity (60%), Stx2 is associated with more severe disease. The relative potencies of five purified Stx2 subtypes, Stx2a, Stx2b, Stx2c, Stx2d, and activated (elastase-cleaved) Stx2d, were studied in vitro and in vivo. In both primary human renal proximal tubule epithelial cells and Vero (monkey kidney cells) cells, Stx2a, Stx2d, and activated Stx2d were at least 25 times more potent than Stx2b and Stx2c. In mice Stx2b and Stx2c had potencies similar to that of Stx1, while Stx2a, Stx2d, and activated Stx2d were 40 to 400 times more potent than Stx1.
Alison Weiss, Ph.D. (Committee Chair)
Rhett Kovall, Ph.D. (Committee Member)
William Miller, Ph.D. (Committee Member)
John Monaco, Ph.D. (Committee Member)
Jane Strasser, Ph.D. (Committee Member)
141 p.
Microbiology
Shiga toxin; Shiga toxin producing E coli; HUS; bacterial toxins; STEC

Recommended Citations

Citations

  • Pellino, C. A. (2014). Characterization of Shiga Toxin Potency and Assembly [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1418909563

    APA Style (7th edition)

  • Pellino, Christine. Characterization of Shiga Toxin Potency and Assembly. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1418909563.

    MLA Style (8th edition)

  • Pellino, Christine. "Characterization of Shiga Toxin Potency and Assembly." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1418909563

    Chicago Manual of Style (17th edition)

ucin1418909563
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This open access ETD is published by University of Cincinnati and OhioLINK.