Investigation of parasporins, the cytotoxic proteins from the bacterium Bacillus thuringiensis

Krishnan, Vidisha (2013) Investigation of parasporins, the cytotoxic proteins from the bacterium Bacillus thuringiensis. Doctoral thesis (PhD), University of Sussex.

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Abstract

The cytotoxic activities of proteins from the normally insecticidal Bacillus thuringiensis against human cancer cell lines were investigated. Cry41Aa toxin derived from the Bacillus thuringiensis strain A1462, which shows activity against human cancer cell lines is structurally related to the toxins synthesized by commercially produced transgenic insect-resistant plants, with the exception of an additional C-terminal beta-trefoil ricin domain. To test whether this putative carbohydrate binding domain is responsible for the cytotocidal activity of Cry41Aa against cancer cell lines, we developed an efficient expression system for the toxin and created a deletion mutant lacking the ricin domain. Both Cry41Aa and its deletion mutant were stably expressed and found to have almost identical activities against the HepG2 cancer cell line in vitro. Our results suggest that the acquisition of the ricin domain was not responsible for Cry41Aa having toxicity to human cancer cells and more subtle changes have resulted in the evolution of mammalian cancer cell toxicity. We further attempted to identify those differences that are responsible for the divergence in activity between the cancer-killing toxins and their insecticidal counterparts. We also studied the cell-killing activity of other uncharacterized Bacillus thuringiensis crystal toxins including Cry51 and Cry65 whose targets are not known so far.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Library Cataloguing
Date Deposited: 06 Dec 2013 07:55
Last Modified: 17 Sep 2015 13:28
URI: http://sro.sussex.ac.uk/id/eprint/47169

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