Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems

Toxins

Nicholas C. Butzin¹  Roderick V. Jensen²  Heather S. Deter³  William H. Mather⁴ 

[1] Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57006, USA;Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0435, USA;Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0435, USA;Quantitative Biosciences, Inc., Solana Beach, CA 92075, USA;

关键词: toxin–antitoxin systems;    persister;    RNA-seq;    ribosome profiling;    Ribo-Seq;   

DOI  :  10.3390/toxins9070211

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown