Dissecting the function of the HigB addiction module toxin

Abstract

Toxin‐antitoxin (TA) modules were initially discovered on bacterial plasmids that facilitate plasmid maintenance via post segregational killing. More recently, chromosomally encoded TA operons found in free‐living prokaryotes have been demonstrated to aid in the cellular response to stress. TA modules encode a stable toxin that inhibits cellular growth, and a labile cognate antitoxin, that inhibits the action of the toxin through the formation of a toxin/antitoxin complex. In addition, these modules have been implicated in pathogenesis and antibiotic tolerance. TA systems also represent a new class of targets for antibiotic treatment of pathogens resistant to existing therapeutics.The goal of this project is to identify the precise function and intracellular target of the HigB toxin, which is a member of the RelE family of toxins. When expressed, RelE or HigB inhibit protein translation through mRNA cleavage that is mediated by the association of the toxins with the Escherichia coli 50S ribosomal subunit. However, the specificity of mRNA cleavage and the nature of the ribosome‐dependent toxin activity appear to be distinct between the two toxins. We are currently investigating additional mechanistic details of HigB toxicity. Research supported by the Virus‐Host Interactions in Eukaryotic Cells T32 Training Grant from the NIH‐NIAID awarded to Dr. Sidney Pestka.