The small RNA SgrS: roles in metabolism and pathogenesis of enteric bacteria

Abstract

Bacteria adapt to ever-changing habitats through specific responses to internal and external stimuli that result in changes in gene regulation and metabolism. One internal metabolic cue affecting such changes in Escherichia coli and related enteric species is cytoplasmic accumulation of phosphorylated sugars such as glucose-6-phosphate or the non-metabolizable analog α-methylglucoside-6-phosphate. This “glucose-phosphate stress” triggers a dedicated stress response in γ-proteobacteria including several enteric pathogens. The major effector of this stress response is a small RNA (sRNA), SgrS. In E. coli and Salmonella, SgrS regulates numerous mRNA targets via base pairing interactions that result in alterations in mRNA translation and stability. Regulation of target mRNAs allows cells to reduce import of additional sugars and increase sugar efflux. SgrS is an unusual sRNA in that it also encodes a small protein, SgrT, which inhibits activity of the major glucose transporter. The two functions of SgrS, base pairing and production of SgrT, reduce accumulation of phosphorylated sugars and thereby relieve stress and promote growth. Examination of SgrS homologs in many enteric species suggests that SgrS has evolved to regulate distinct targets in different organisms. For example, in Salmonella, SgrS base pairs with sopD mRNA and represses production of the encoded effector protein, suggesting that SgrS may have a specific role in the pathogenesis of some γ-proteobacteria. In this review, we outline molecular mechanisms involved in SgrS regulation of its target mRNAs. We also discuss the response to glucose-phosphate stress in terms of its impact on metabolism, growth physiology, and pathogenesis.

Multiple ways to regulate translation initiation in bacteria: Mechanisms, regulatory circuits, dynamics

“…E. coli SgrS sRNA is produced during glucose-phosphate stress, which is characterized by the accumulation of phosphosugars like glucose 6-phosphate (reviewed in Ref. [176]). SgrS negatively regulates the translation of ptsG mRNA via base pairing interactions with the RBS in an Hfqdependent manner and stimulates the rapid degradation of the repressed mRNA by an RNase E-dependent mechanism [177,178].…”

Dual-Function RNAs

“…Glucose phosphate stress occurs when sugar transport and metabolism become uncoupled. This can occur in certain mutant strains (26, 27) or in wild-type strains that take up the non-metabolizable sugar analogs α-methylglucoside (αMG) and 2-deoxyglucose (2DG) (3, 25). Accumulation of sugar phosphates or their analogs and depletion of other glycolytic intermediates results in growth inhibition (28).…”

“…For this category of sRNAs, base-pairing interactions occlude the ribosome binding site (RBS) of the mRNA and thus inhibit translation initiation (3, 4). There is also a small subset of sRNAs that stabilize transcripts that are otherwise prone to degradation by cellular RNases (5, 6).…”

The Staphylococcus aureus Protein-Coding Gene gdpS Modulates sarS Expression via mRNA-mRNA Interaction

“…Dual-function RNAs are not very common, and only a few examples have been reported (28). For example, E. coli RNA SgrS can regulate several mRNA targets through direct base pairing and encodes the 43-amino-acid polypeptide SgrT (29). The 39-amino-acid peptide SR1P, encoded by SR1 RNA, was also detected from a multicopy plasmid by Western blotting in Bacillus subtilis (30).…”