Chapter title |
Isolation and Analysis of Suppressor Mutations in Tumor-Targeted msbB Salmonella
|
---|---|
Chapter number | 10 |
Book title |
Bacterial Therapy of Cancer
|
Published in |
Methods in molecular biology, January 2016
|
DOI | 10.1007/978-1-4939-3515-4_10 |
Pubmed ID | |
Book ISBNs |
978-1-4939-3513-0, 978-1-4939-3515-4
|
Authors |
K. Brooks Low, Sean R. Murray, John Pawelek, David Bermudes |
Abstract |
Tumor-targeted Salmonella offers a promising approach to the delivery of therapeutics for the treatment of cancer. The Salmonella strains used, however, must be stably attenuated in order to provide sufficient safety for administration. Approaches to the generation of attenuated Salmonella strains have included deletion of the msbB gene that is responsible for addition of the terminal myristol group to lipid A. In the absence of myristoylation, lipid A is no longer capable of inducing septic shock, resulting in a significant enhancement in safety. However, msbB Salmonella strains also exhibit an unusual set of additional physiological characteristics, including sensitivities to NaCl, EGTA, deoxycholate, polymyxin, and CO2. Suppressor mutations that compensate for these sensitivities include somA, Suwwan, pmrA (C) , and zwf. We describe here methods for isolation of strains with compensatory mutations that suppress these types of sensitivities and techniques for determining their underlying genetic changes and analysis of their effects in murine tumor models. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 6 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 2 | 33% |
Student > Master | 2 | 33% |
Student > Doctoral Student | 1 | 17% |
Student > Bachelor | 1 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 3 | 50% |
Chemical Engineering | 1 | 17% |
Engineering | 1 | 17% |
Unknown | 1 | 17% |