# Extracytoplasmic Function \(\sigma\) Factors as Tools for Coordinating Stress Responses
## 1 Introduction and Aim of this Review  
Bacteria, like all other living organisms, have adapted and evolved to inhabit a specific environment, tuning their physiology and metabolism to the pervading conditions provided by their habitat. However, bacteria also need to be prepared to face constant changes in their environment. These fluctuations may lead to important deviations from the optimal growth conditions for a species, threatening bacterial survival, and are known as stress conditions. Stress may be generated by environmental changes and by the biochemical processes performed in the cell, although it may also appear as nutrient starvation or interactions with a host. Furthermore, a stress-inducing condition is subjective and specific for each species, so that different bacterial representatives may differ in their response to the same stimulus. When the conditions shift to a less favorable situation, bacteria fight for survival by activating a number of mechanisms and regulatory circuits whose main effect is the mitigation, or removal, of the stress. The gene products synthesized to overcome stress conditions are variable depending on the stress. For example, temperature shifts may lead to the production of chaperones that aid in protein folding and proteases to remove misfolded proteins [1]. These shifts can also result in the production of proteins involved in maintaining the fluidity and functionality of the cell membrane [2]. Oxidative stress can be overcome by expressing catalases or peroxideroxins [3, 4], which catalyze the conversion of ROS (reactive oxygen species) into harmless compounds before they can damage cellstructures. Alternatively, the response can result in the production of components that repair already damaged proteins, such as thioredoxinins and glutaredoxins [5; 6]. The host immune system, which is activated upon bacterial infection, can also be considered a stress for a pathogen and can result in activation of mechanisms to evade the host defenses [7]. These are the so-called bacterial stress responses, which comprise sensing of the stress and the ultimate activation of the resistance system through a signal transduction process. Actually, any type of bacterial signal transduction mechanism (reviewed in [8]) may be used to exert these responses, as long as its goal is to prepare the cell to face a threatening situation. However, from a classical point of view, bacterial signaling is performed by one- and two-component systems (OCSs and TCSs, respectively), which may introduce the added complexity of a phosphorelay when more than one phosphotransfer step occurs. Recently, Ser/Thr kinase systems started to gain relevance in the bacterial world, since they were originally thought to have a minor role compared to their functions in _Eukarya_[9]. This occurs despite sharing a common evolutionary origin [10] and contrasting with the His/Asp kinase/phosphotransfer mechanisms on which most TCSs rely. Besides these mechanisms to regulate the activation of stress responses, alternative \(\sigma\) factors can also be used by bacteria. \(\sigma\) factors are subunits of the RNA polymerase (RNAP) holoenzyme essential for transcription initiation, due to their role in guiding the catalytic core of the RNAP in promoter recognition. Moreover, their specific helicase activity on the -10 box facilitates the formation of the transcription bubble through formation of the open complex. Apart from the vegetative \(\sigma^{70}\) factor, which ensure the bulk of the transcriptional control of house-keeping genes, alternative \(\sigma\) factors control the expression of a number of specific genes (regulons) with a defined collective function, which may go beyond the stress response. In the early 1990s, certain representatives of this group caught the attention of molecular microbiologists (reviewed in [11]) because of their small size. They comprise the essential domains allowing RNAP interaction, promoter-binding and initiation activity.