Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution

Abstract

Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2–4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor.

The essential activities of the bacterial sigma factor

“…Many factors (particularly Group IV proteins) are negatively regulated by membrane or cytoplasmic proteins called anti-factors (Missiakas and Raina 1998;Helmann 1999;Paget 2015). In the absence of a specific environmental cue, anti-factors bind and sequester factors from core RNAP.…”

“…In the absence of a specific environmental cue, anti-factors bind and sequester factors from core RNAP. With the imposition of a specific physicochemical signal, anti-factor function is abrogated through targeted proteolysis (Heinrich and Wiegert 2009), by structural modification (Kang et al 1999;Paget 2015), or by the action of an anti-anti-factor (Pané-Farré et al 2005;Francez-Charlot et al 2009), and the factor is released into the cytoplasm and available for holoenzyme formation and transcription. Either directly or indirectly, anti-factors are important modules for sensory perception in bacteria.…”

Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors

“…A number of excellent reviews cover these topics, and the reader is referred to them for further information [30, 32–37]. Nevertheless, a very brief introduction to ECF sigma factors will be necessary before delving into the specifics of how ECF sigma factors regulate antimicrobial resistance.…”

Loss of σI affects heat-shock response and virulence gene expression in Bacillus anthracis

“…Many sigma factors are regulated post-translationally by anti-sigma factors that bind to the sigma factor and prevent its interaction with RNAP. The anti-sigma factor is released in response to cellular signals, freeing the sigma factor to interact with RNAP to direct transcription of target genes (Paget, 2015). Of the 27 predicted sigma factors in the B. anthracis genome (Schmidt et al, 2011), only a small number have been studied experimentally: s B is involved in the heat-shock response and influences virulence in a mouse model of infection (Fouet et al, 2000), s H is required for sporulation and influences toxin gene expression in some B. anthracis strains (Bongiorni et al, 2008;Hadjifrangiskou et al, 2007), and s P controls b-lactamase in a penicillin-resistant B. anthracis strain (Ross et al, 2009).…”