The σB-Mediated General Stress Response of Listeria monocytogenes: Life and Death Decision Making in a Pathogen

Abstract

Sensing and responding to environmental cues is critical for the adaptability and success of the food-borne bacterial pathogen Listeria monocytogenes. A supramolecular multiprotein complex known as the stressosome, which acts as a stress sensing hub, is responsible for orchestrating the activation of a signal transduction pathway resulting in the activation of σ B , the sigma factor that controls the general stress response (GSR). When σ B is released from the anti-sigma factor RsbW, a rapid up-regulation of the large σ B regulon, comprised of ≥ 300 genes, ensures that cells respond appropriately to the new environmental conditions. A diversity of stresses including low pH, high osmolarity, and blue light are known to be sensed by the stressosome, resulting in a generalized increase in stress resistance. Appropriate activation of the stressosome and deployment of σ B are critical to fitness as there is a trade-off between growth and stress protection when the GSR is deployed. We review the recent developments in this field and describe an up-to-date model of how this sensory organelle might integrate environmental signals to produce an appropriate activation of the GSR. Some of the outstanding questions and challenges in this fascinating field are also discussed.

STAS Domain Only Proteins in Bacterial Gene Regulation

“…The anti-sigma factor RsbW, which normally sequesters σ B , binds dephosphorylated RsbV with a higher affinity than RsbW, freeing σ B to initiate transcription of its operon. This complex regulatory system contributes to survival of L. monocytogenes , both inside and outside the host, by affecting its virulence and survival under environmental stress, respectively ( Chaturongakul and Boor, 2004 ; Chaturongakul and Boor, 2006 ; Shin et al., 2010 ; Utratna et al., 2014 ; O’Donoghue et al, 2016 ; Guerreiro et al., 2020a ; Guerreiro et al., 2020b ; Hsu et al., 2020 ).…”

Alternative σ Factors Regulate Overlapping as Well as Distinct Stress Response and Metabolic Functions in Listeria monocytogenes under Stationary Phase Stress Condition

“…Phenotypic contributions of σ C , σ H , and σ L to L. monocytogenes stress resistance have been challenging to define, however, and in some studies, no clear effects of deletions in these genes, on different stress-response phenotypes, have been observed [ 12 ]. On the other hand, σ B clearly shows robust contributions to L. monocytogenes survival or growth under salt stress, acid stress, oxidative stress, and starvation, as supported by a number of studies [ 11 , 12 , 15 , 19 , 20 , 21 ] and as summarized in recent reviews [ 16 , 22 ]. Importantly, σ B also plays a role in regulating virulence-related functions [ 17 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Comparative Review of the Responses of Listeria monocytogenes and Escherichia coli to Low pH Stress

“…In L. monocytogenes , σ B is regulated by a signaling cascade composed by several proteins (RsbR, RsbS, RsbT, RsbU, RsbV, RsbW, and RsbX) (reviewed recently in [ 8 , 106 ]), and when activated it results in the upregulation of approximately 300 genes [ 107 , 108 , 109 ] that increase L. monocytogenes resistance towards lethal acid stress [ 23 , 25 , 26 , 110 ]. Several acid resistance related genes, including argA , argR , gadD1 , and gadD3 are regulated by σ B [ 16 , 28 , 111 , 112 ] ( Figure 1 B).…”

“…We also review the acid tolerance mechanisms of Listeria monocytogenes , a Gram-positive rod that belongs to the division Firmicutes, which is very well studied for its role as an intracellular food-borne pathogen of humans and cattle. In nature, L. monocytogenes is a saprophyte and is characterized by its tolerance to stresses such as low pH, elevated osmolarity, and bile salts and its ability to grow at refrigeration temperatures [ 6 , 7 , 8 ]. While these bacteria are phylogenetically unrelated, they share the ability to enter the host via contaminated food or water, and therefore both can encounter the gastrointestinal environment, including the extreme acid conditions prevailing in the stomach, as part of their life cycles.…”