Protection against deleterious nitrogen compounds: role of σ<sup>S</sup>-dependent small RNAs encoded adjacent to<i>sdiA</i>

Hao, Yue; Updegrove, Taylor B.; Livingston, Natasha N.; Storz, Gisela

doi:10.1093/nar/gkw404

Cited by 41 publications

(41 citation statements)

References 51 publications

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“…SdsR is an enterobacterial core sRNA and an integral part of the large regulon controlled by the stationary phase sigma factor, σ S (40). Additional bacterial regulators such as GadY, SraL and SdsN sRNAs are also controlled by σ S (78–80), and recent experiments in E. coli identified σ S -binding to the promoter sequences of the two Hfq-dependent sRNAs, SdsR and OmrA (81). OmrA is a regulator of membrane homeostasis and biofilm formation in E. coli and, in addition to σ S , transcription of omrA is controlled by the EnvZ/OmpR TCS (82–84).…”

Section: Discussionmentioning

confidence: 99%

The target spectrum of SdsR small RNA inSalmonella

et al. 2016

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Model enteric bacteria such as Escherichia coli and Salmonella enterica express hundreds of small non-coding RNAs (sRNAs), targets for most of which are yet unknown. Some sRNAs are remarkably well conserved, indicating that they serve cellular functions that go beyond the necessities of a single species. One of these ‘core sRNAs’ of largely unknown function is the abundant ∼100-nucleotide SdsR sRNA which is transcribed by the general stress σ-factor, σS and accumulates in stationary phase. In Salmonella, SdsR was known to inhibit the synthesis of the species-specific porin, OmpD. However, sdsR genes are present in almost all enterobacterial genomes, suggesting that additional, conserved targets of this sRNA must exist. Here, we have combined SdsR pulse-expression with whole genome transcriptomics to discover 20 previously unknown candidate targets of SdsR which include mRNAs coding for physiologically important regulators such as the carbon utilization regulator, CRP, the nucleoid-associated chaperone, StpA and the antibiotic resistance transporter, TolC. Processing of SdsR by RNase E results in two cellular SdsR variants with distinct target spectra. While the overall physiological role of this orphan core sRNA remains to be fully understood, the new SdsR targets present valuable leads to determine sRNA functions in resting bacteria.

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Section: Discussionmentioning

confidence: 99%

The target spectrum of SdsR small RNA inSalmonella

et al. 2016

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“…It is possible that the different versions act on different sets of mRNAs targets or by different mechanisms (91, 94). Hints of such nuanced regulation are coming from global analyses of sRNA-mRNA pairs where different sets of targets are observed for different forms of a sRNAs (84, 95).…”

Section: Other Types Of Multifunctional Srnas/mrnasmentioning

confidence: 99%

Dual-Function RNAs

et al. 2018

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Bacteria are known to use RNA, either as mRNAs encoding proteins or as non-coding small RNAs (sRNAs), to regulate numerous biological processes. However, a few sRNAs have two functions: they act as base pairing RNAs and encode a small protein with additional regulatory functions. Thus, these so called “dual-function” sRNAs can serve as both a riboregulator and an mRNA. In some cases, these two functions can act independently within the same pathway while in other cases, the base-pairing function and protein function act in different pathways. Here, we discuss the five known dual-function sRNAs: SgrS from enteric species, RNAIII and Psm-mec from Staphylococcus aureus, Pel RNA from Streptococcus pyogenes, and SR1 from Bacillus subtilis, and review their mechanisms of action and roles in regulating diverse biological processes. We also discuss the prospect of finding additional dual-function sRNAs and future challenges in studying the overlap and competition between the functions.

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“…Given the defective output from both the hmpp and katGp transcriptional reporters, we performed experiments to assess the involvement of known regulators of hmp or katG expression. FNR and Fur have been identified as regulators of both hmp and katG, whereas NsrR, RpoS, SdsN, and MetR have been implicated in the regulation of hmp and OxyR in the regulation of katG (39,(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). In addition, we assessed the involvement of DksA, the stringent response regulator, which has recently emerged as a regulator of oxidative and nitrosative stresses in Salmonella enterica (56)(57)(58)(59) and that we have identified as important for expression of Hmp in E. coli (60).…”

Section: And Fig S4) (See Materials and Methods)mentioning

confidence: 99%

Transcriptional Regulation Contributes to Prioritized Detoxification of Hydrogen Peroxide over Nitric Oxide

2019

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Hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO·) are toxic metabolites that immune cells use to attack pathogens. These antimicrobials can be present at the same time in phagosomes, and it remains unclear how bacteria deal with these insults when simultaneously present. Here, using Escherichia coli, we observed that simultaneous exposure to H 2 O 2 and NO· leads to prioritized detoxification, where enzymatic removal of NO· is impeded until H 2 O 2 has been eliminated. This phenomenon is reminiscent of carbon catabolite repression (CCR), where preferred carbon sources are catabolized prior to less desirable substrates; however, H 2 O 2 and NO· are toxic, growth-inhibitory compounds rather than growth-promoting nutrients. To understand how NO· detoxification is delayed by H 2 O 2 whereas H 2 O 2 detoxification proceeds unimpeded, we confirmed that the effect depended on Hmp, which is the main NO· detoxification enzyme, and used an approach that integrated computational modeling and experimentation to delineate and test potential mechanisms. Plausible interactions included H 2 O 2 -dependent inhibition of hmp transcription and translation, direct inhibition of Hmp catalysis, and competition for reducing equivalents between Hmp and H 2 O 2 -degrading enzymes. Experiments illustrated that Hmp catalysis and NAD(P)H supply were not impaired by H 2 O 2 , whereas hmp transcription and translation were diminished. A dependence of this phenomenon on transcriptional regulation parallels CCR, and we found it to involve the transcriptional repressor NsrR. Collectively, these data suggest that bacterial regulation of growth inhibitor detoxification has similarities to the regulation of growth substrate consumption, which could have ramifications for infectious disease, bioremediation, and biocatalysis from inhibitor-containing feedstocks. IMPORTANCE Bacteria can be exposed to H 2 O 2 and NO· concurrently within phagosomes. In such multistress situations, bacteria could have evolved to simultaneously degrade both toxic metabolites or preferentially detoxify one over the other. Here, we found that simultaneous exposure to H 2 O 2 and NO· leads to prioritized detoxification, where detoxification of NO· is hampered until H 2 O 2 has been eliminated. This phenomenon resembles CCR, where bacteria consume one substrate over others in carbon source mixtures. Further experimentation revealed a central role for transcriptional regulation in the prioritization of H 2 O 2 over NO·, which is also important to CCR. This study suggests that regulatory scenarios observed in bacterial consumption of growth-promoting compound mixtures can be conserved in bacterial detoxification of toxic metabolite mixtures.

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Protection against deleterious nitrogen compounds: role of σ^S-dependent small RNAs encoded adjacent tosdiA

Cited by 41 publications

References 51 publications

The target spectrum of SdsR small RNA inSalmonella

The target spectrum of SdsR small RNA inSalmonella

Dual-Function RNAs

Transcriptional Regulation Contributes to Prioritized Detoxification of Hydrogen Peroxide over Nitric Oxide

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Protection against deleterious nitrogen compounds: role of σS-dependent small RNAs encoded adjacent tosdiA

Cited by 41 publications

References 51 publications

The target spectrum of SdsR small RNA inSalmonella

The target spectrum of SdsR small RNA inSalmonella

Dual-Function RNAs

Transcriptional Regulation Contributes to Prioritized Detoxification of Hydrogen Peroxide over Nitric Oxide

Contact Info

Product

Resources

About

Protection against deleterious nitrogen compounds: role of σ^S-dependent small RNAs encoded adjacent tosdiA