RNA Regulated Toxin-Antitoxin Systems in Pathogenic Bacteria.

David D Sarpong,Erin R Murphy

doi:10.3389/fcimb.2021.661026

David D Sarpong, Erin R Murphy

Open Access

https://doi.org/10.3389/fcimb.2021.661026

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Abstract

The dynamic host environment presents a significant hurdle that pathogenic bacteria must overcome to survive and cause diseases. Consequently, these organisms have evolved molecular mechanisms to facilitate adaptation to environmental changes within the infected host. Small RNAs (sRNAs) have been implicated as critical regulators of numerous pathways and systems in pathogenic bacteria, including that of bacterial Toxin-Antitoxin (TA) systems. TA systems are typically composed of two factors, a stable toxin, and a labile antitoxin which functions to protect against the potentially deleterious activity of the associated toxin. Of the six classes of bacterial TA systems characterized to date, the toxin component is always a protein. Type I and Type III TA systems are unique in that the antitoxin in these systems is an RNA molecule, whereas the antitoxin in all other TA systems is a protein. Though hotly debated, the involvement of TA systems in bacterial physiology is recognized by several studies, with the Type II TA system being the most extensively studied to date. This review focuses on RNA-regulated TA systems, highlighting the role of Type I and Type III TA systems in several pathogenic bacteria.

Highlights

At each point in the transmission and infection cycle, pathogenic bacteria are presented with various, and often extreme environmental conditions to which they must quickly adapt to survive
Pathogenic bacteria have evolved a variety of mechanisms by which to adapt to environmental changes, many of which involve protein factors that regulate the expression of a specific gene(s) in response to specific environmental signals (Brooks et al, 2011)
An increasing number of studies, have revealed the vast potential of small RNAs in controlling complex regulatory circuits connected to bacterial survival and/or virulence

Summary

INTRODUCTION

At each point in the transmission and infection cycle, pathogenic bacteria are presented with various, and often extreme environmental conditions to which they must quickly adapt to survive. One role that sRNAs play in controlling bacterial physiology and virulence is that of the anti-toxin component of Type I and Type III Toxin-Antitoxin (TA) systems (Brantl and Jahn, 2015; Holmqvist and Wagner, 2017). Type I and III TA systems involve sRNA antitoxins which either repress the translation (Type I) or activity (Type III) of the associated toxin protein. The newly discovered Type VI TA system involves an antitoxin protein which promotes toxin degradation by recruiting a protease to cleave it (Unterholzner et al, 2013; Harms et al, 2018; Song and Wood, 2020b). Numerous studies have linked bacteria survival and pathogenesis to TA systems (Lobato-Márquez et al, 2015; Fernández-Garcıá et al, 2016; Lobato-Márquez et al, 2016a). We highlight Type I and Type III TA systems and the role they play in the survival, pathogenicity, and persistence of select bacterial pathogens

SECTION 1: TYPE I TOXIN ANTITOXIN SYSTEMS

SECTION 2: TYPE III TOXIN ANTITOXIN SYSTEMS