title: Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications.
abstract: 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.
authors.affiliation: Biomedical Research Centre, Faculty of Medicine, Universiti Sultan Zainal Abidin, Medical Campus, Jalan Sultan Mahmud, 20400 Kuala Terengganu, Malaysia. chewchieng@gmail.com.
authors.forename: Chew Chieng
authors.initials: CC
authors.lastname: Yeo
authors.affiliation: Centre for Research in Biotechnology for Agriculture (CEBAR) and Institute for Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. afung87@gmail.com.
authors.forename: Fauziah
authors.initials: F
authors.lastname: Abu Bakar
authors.affiliation: Molecular Microbiology and Infection Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Ramiro de Maeztu 9, 28040 Madrid, Spain. chanyting@hotmail.com.
authors.forename: Wai Ting
authors.initials: WT
authors.lastname: Chan
authors.affiliation: Molecular Microbiology and Infection Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Ramiro de Maeztu 9, 28040 Madrid, Spain. mespinosa@cib.csic.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Espinosa
authors.affiliation: Centre for Research in Biotechnology for Agriculture (CEBAR) and Institute for Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. jennihari@um.edu.my.
authors.forename: Jennifer Ann
authors.initials: JA
authors.lastname: Harikrishna
mesh_terms: D000818:Animals; D000992:Antitoxins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D005057:Eukaryotic Cells / Q000378:metabolism; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D015003:Yeasts / Q000235:genetics
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins
keywords: anticancer therapy; antiviral therapy; cell ablation; gene containment; gene therapy; genetic manipulation; high expression cell lines; toxin-antitoxin systems