Regulation of growth and death in Escherichia coli by toxin–antitoxin systems

The toxin–antitoxin (TA) systems of bacteria are new-comers in microbiology and biochemistry, as most of the discoveries about these systems have been made in the past decade. To date, it has been revealed that most bacteria and many archaea contain a number of highly diverse TA systems in their genomes.In the type II TA systems, a toxin is constitutively co-expressed with its cognate antitoxin from a TA operon to form a stable complex in normally growing cells. As the antitoxin is less stable than the toxin in the cell, antitoxin has to be constantly produced to neutralize the cognate toxin. Under stress conditions, antitoxins are degraded by stress-induced proteases to release free toxins in the cells, resulting in cell growth arrest and eventual cell death.Cellular targets of TA systems are highly diverse, from DNA replication to mRNA stability, protein synthesis, ATP production and cell wall biosynthesis. Other cellular targets are likely to be identified as more TA systems are discovered. The most frequent cellular targets for the Escherichia coli TA systems are mRNAs, perhaps because the inhibition of mRNA function seems to be the mildest means of regulating cell growth. Out of 36 TA systems in E. coli, 11 are known to interfere with mRNA.As toxins targeting mRNA cleave cellular mRNAs, they are termed mRNA interferases. These mRNA interferases are grouped into two distinct classes depending on how they cleave mRNAs: ribosome-independent mRNA interferases and ribosome-dependent mRNA interferases (which cleave mRNAs at the ribosomal A site).It has been shown that some toxins are induced under several stress conditions, including amino acid starvation, glucose starvation, DNA damage, heat and the addition of antibiotics; these toxins regulate cell growth, triggering programmed cell death. It is also predicted that the induction of some toxins is able to cause the persistent or quasi-dormant state, making these cells resistant to antibiotics. The toxins may also play a part in eliminating damaged cells from their populations.Elucidation of the functions of these toxins is essential for our understanding of their roles in bacterial physiology under various stress conditions and also their roles in bacterial pathogenicity. The study of TA systems opens the door into a new and exciting field in medical research, molecular biology and biotechnology, as various toxins from TA systems may be used as new therapeutic tools. TA systems may also provide novel technologies for gene regulation and protein production.