Type II Toxin-Antitoxin Loci, hipBA and Persisters

Persisters are dormant cells responsible for drug tolerance of chronic infections. Persisters can be produced stochastically and make up a small subpopulation of cells. Mechanisms of dormancy appear to be highly redundant, and Toxin/Antitoxin (TA) modules have been linked to persister formation. Interferases (mRNA endonucleases) RelE or MazF cause stasis and multidrug tolerance when expressed topically, and deletion of multiple interferases in E. coli decreases the level of persisters. In this chapter, we mainly focus on description of the HipA and TisB toxins. HipA has served as a model for the study of persisters. HipA is a protein kinase, which phosphorylates EF-Tu, inhibiting protein synthesis and causing dormancy. TisB is a typical antimicrobial peptide and is induced by the SOS response. TisB forms anion channels in the E. coli membrane, causing a drop in pmf and ATP, leading to dormancy.