Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications

• Main Authors: Chew Chieng Yeo, Fauziah Abu Bakar, Wai Ting Chan, Manuel Espinosa, Jennifer Ann Harikrishna
• Format: Article
• Language: English
• Published: MDPI AG 2016-02-01
• Series: Toxins
• Subjects: toxin-antitoxin systems; genetic manipulation; gene containment; cell ablation; high expression cell lines; gene therapy; antiviral therapy; anticancer therapy
• Online Access: http://www.mdpi.com/2072-6651/8/2/49

Toxin-antitoxin (TA) systems are found in nearly all prokaryotic genomes and usually consist of a pair of co-transcribed genes, one of which encodes a stable toxin and the other, its cognate labile antitoxin. Certain environmental and physiological cues trigger the degradation of the antitoxin, causing activation of the toxin, leading either to the death or stasis of the host cell. TA systems have a variety of functions in the bacterial cell, including acting as mediators of programmed cell death, the induction of a dormant state known as persistence and the stable maintenance of plasmids and other mobile genetic elements. Some bacterial TA systems are functional when expressed in eukaryotic cells and this has led to several innovative applications, which are the subject of this review. Here, we look at how bacterial TA systems have been utilized for the genetic manipulation of yeasts and other eukaryotes, for the containment of genetically modified organisms, and for the engineering of high expression eukaryotic cell lines. We also examine how TA systems have been adopted as an important tool in developmental biology research for the ablation of specific cells and the potential for utility of TA systems in antiviral and anticancer gene therapies.