Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems

TR Number
Date
2017-07-04
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract

Toxin–antitoxin (TA) systems are key regulators of bacterial persistence, a multidrug-tolerant state found in bacterial species that is a major contributing factor to the growing human health crisis of antibiotic resistance. Type II TA systems consist of two proteins, a toxin and an antitoxin; the toxin is neutralized when they form a complex. The ratio of antitoxin to toxin is significantly greater than 1.0 in the susceptible population (non-persister state), but this ratio is expected to become smaller during persistence. Analysis of multiple datasets (RNA-seq, ribosome profiling) and results from translation initiation rate calculators reveal multiple mechanisms that ensure a high antitoxin-to-toxin ratio in the non-persister state. The regulation mechanisms include both translational and transcriptional regulation. We classified E. coli type II TA systems into four distinct classes based on the mechanism of differential protein production between toxin and antitoxin. We find that the most common regulation mechanism is translational regulation. This classification scheme further refines our understanding of one of the fundamental mechanisms underlying bacterial persistence, especially regarding maintenance of the antitoxin-to-toxin ratio.

Description
Keywords
toxin–antitoxin systems, persister, RNA-seq, ribosome profiling, Ribo-Seq
Citation
Deter, H.S.; Jensen, R.V.; Mather, W.H.; Butzin, N.C. Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems. Toxins 2017, 9, 211.