LytTR Regulatory Systems: A potential new class of prokaryotic sensory system.

Zhengzhong Zou,Jess A Millar,Rahul Raghavan,Jens Kreth,Justin Merritt,Hua Qin,Amanda E Brenner,Zhoujie Xie,Qiang Gu

doi:10.1371/journal.pgen.1007709

Abstract

The most commonly studied prokaryotic sensory signal transduction systems include the one-component systems, phosphosignaling systems, extracytoplasmic function (ECF) sigma factor systems, and the various types of second messenger systems. Recently, we described the regulatory role of two separate sensory systems in Streptococcus mutans that jointly control bacteriocin gene expression, natural competence development, as well as a cell death pathway, yet they do not function via any of the currently recognized signal transduction paradigms. These systems, which we refer to as LytTR Regulatory Systems (LRS), minimally consist of two proteins, a transcription regulator from the LytTR Family and a transmembrane protein inhibitor of this transcription regulator. Here, we provide evidence suggesting that LRS are a unique uncharacterized class of prokaryotic sensory system. LRS exist in a basal inactive state. However, when LRS membrane inhibitor proteins are inactivated, an autoregulatory positive feedback loop is triggered due to LRS regulator protein interactions with direct repeat sequences located just upstream of the -35 sequences of LRS operon promoters. Uncharacterized LRS operons are widely encoded by a vast array of Gram positive and Gram negative bacteria as well as some archaea. These operons also contain unique direct repeat sequences immediately upstream of their operon promoters indicating that positive feedback autoregulation is a globally conserved feature of LRS. Despite the surprisingly widespread occurrence of LRS operons, the only characterized examples are those of S. mutans. Therefore, the current study provides a useful roadmap to investigate LRS function in the numerous other LRS-encoding organisms.

Highlights

The capacity of bacteria to sense and respond to stimuli triggered by the extracellular environment is fundamental for survival, in highly dynamic and/or competitive niches
Defining LytTR Regulatory Systems current study, we provide the first evidence for the existence of a potentially new class of prokaryotic sensory system, which we refer to as LytTR Regulatory Systems (LRS)
We show that LRS are broadly distributed among prokaryotes and are distinct from the other commonly studied sensory systems like two-component signal transduction systems and extracytoplasmic function (ECF) sigma factor systems

Summary

Introduction

The capacity of bacteria to sense and respond to stimuli triggered by the extracellular environment is fundamental for survival, in highly dynamic and/or competitive niches. The vast majority of one-component systems are soluble proteins that utilize a diverse array of small molecules to modulate their transcription factor activity [1]. Among the best characterized classes of prokaryotic sensory systems are the phosphosignaling systems, exemplified by two-component signal transduction systems (TCSTS) and eukaryotic-like serine-threonine kinases/phosphatases (eSTK/P). Unlike TCSTS and eSTK/P, ECF systems do not typically encode enzymatic domains within sensor proteins; rather, gene expression is regulated through the production of alternative σ factors that dictate the promoter affinity of RNA polymerase [9, 10]. For (p)ppGpp, its synthesis is catalyzed by RelA-SpoT family enzymes [22] Once created, these second messengers can bind directly to their target proteins or RNAs to modulate their functions [20, 23, 24]

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