Control of RNA Stability by NrrF, an Iron-Regulated Small RNA in Neisseria gonorrhoeae

Jackson, Lydgia A.; Pan, Jinren; Day, Michael; Dyer, David W.

doi:10.1128/jb.00839-13

Cited by 23 publications

(23 citation statements)

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“…MtrF is also by itself a proton motive force (PMF)-dependent antibiotic efflux pump that expels sulfonamides from the bacteria (32). Interestingly, trans-acting, iron-regulated sRNA NrrF directly controls MtrF expression by reducing mtrF mRNA stability by increasing its turnover (33,58). Thus, NrrF attenuates MtrF action in antibiotic resistance.…”

Section: Srnas and Active Drug Effluxmentioning

confidence: 99%

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Bacterial Adaptation to Antibiotics through Regulatory RNAs

Felden

Cattoir

2018

Antimicrob Agents Chemother

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The extensive use of antibiotics has resulted in a situation where multidrug-resistant pathogens have become a severe menace to human health worldwide. A deeper understanding of the principles used by pathogens to adapt to, respond to, and resist antibiotics would pave the road to the discovery of drugs with novel mechanisms. For bacteria, antibiotics represent clinically relevant stresses that induce protective responses. The recent implication of regulatory RNAs (small RNAs [sRNAs]) in antibiotic response and resistance in several bacterial pathogens suggests that they should be considered innovative drug targets. This minireview discusses sRNA-mediated mechanisms exploited by bacterial pathogens to fight against antibiotics. A critical discussion of the newest findings in the field is provided, with emphasis on the implication of sRNAs in major mechanisms leading to antibiotic resistance, including drug uptake, active drug efflux, drug target modifications, biofilms, cell walls, and lipopolysaccharide (LPS) biosynthesis. Of interest is the lack of knowledge about sRNAs implicated in Gram-positive compared to Gram-negative bacterial resistance.

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Section: Srnas and Active Drug Effluxmentioning

confidence: 99%

“…Thus, NrrF attenuates MtrF action in antibiotic resistance. MtrF transcripts are also repressed by Fur, MtrR (repressor of mtrCDE), and MpeR (repressor of mtrR) (33), implying that expression of that inner membrane protein is tightly controlled by several additional regulators.…”

Section: Srnas and Active Drug Effluxmentioning

confidence: 99%

Bacterial Adaptation to Antibiotics through Regulatory RNAs

Felden

Cattoir

2018

Antimicrob Agents Chemother

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“…Fe-deplete (CDM-0) and Fe-replete medium (CDM-10), supplemented with 10 μm Fe (NO 3 ) 3 were prepared as previously reported [16, 52]. Briefly, organisms were inoculated to an OD 600 = 0.100 from overnight growth on GCB agar plates.…”

Section: Methodsmentioning

confidence: 99%

Iron-regulated small RNA expression as Neisseria gonorrhoeae FA 1090 transitions into stationary phase growth

et al. 2017

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BackgroundFor most pathogens, iron (Fe) homeostasis is crucial for maintenance within the host and the ability to cause disease. The primary transcriptional regulator that controls intracellular Fe levels is the Fur (ferric uptake regulator) protein, which exerts its action on transcription by binding to a promoter-proximal sequence termed the Fur box. Fur-regulated transcriptional responses are often fine-tuned at the post-transcriptional level through the action of small regulatory RNAs (sRNAs). Consequently, identifying sRNAs contributing to the control of Fe homeostasis is important for understanding the Fur-controlled bacterial Fe-response network.ResultsIn this study, we sequenced size-selected directional libraries representing sRNA samples from Neisseria gonorrhoeae strain FA 1090, and examined the Fe- and temporal regulation of these sRNAs. RNA-seq data for all time points identified a pool of at least 340 potential sRNAs. Differential analysis demonstrated that expression appeared to be regulated by Fe availability for at least fifteen of these sRNAs. Fourteen sRNAs were induced in high Fe conditions, consisting of both cis and trans sRNAs, some of which are predicted to control expression of a known virulence factor, and one SAM riboswitch. An additional putative cis-acting sRNA was repressed by Fe availability. In the pathogenic Neisseria species, one sRNA that contributes to Fe-regulated post-transcriptional control is the Fur-repressible sRNA NrrF. The expression of five Fe-induced sRNAs appeared to be at least partially controlled by NrrF, while the remainder was expressed independently of NrrF. The expression of the 14 Fe-induced sRNAs also exhibited temporal control, as their expression levels increased dramatically as the bacteria entered stationary phase.ConclusionsHere we report the temporal expression of Fe-regulated sRNAs in N. gonorrhoeae FA 1090 with several appearing to be controlled by the Fe-repressible sRNA NrrF. Temporal regulation of these sRNAs suggests a regulatory role in controlling functions necessary for survival, and may be important for phenotypes often associated with altered growth rates, such as biofilm formation or intracellular survival. Future functional studies will be needed to understand how these regulatory sRNAs contribute to gonococcal biology and pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3684-8) contains supplementary material, which is available to authorized users.

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“…The latter binds and thereby represses tolC mRNA in E. coli and Salmonella [155]. Other examples include MdtEF regulation by DsrA in E. coli [156] and MtrF (part of MtrCDE) regulation by NrrF in Neisseria gonorrhoeae [157]. Furthermore, sRNAs can 're-wire' two component cascades and therewith indirectly influence expression level [158].…”

Section: Tripartite Pump Regulationmentioning

confidence: 99%

Structure and mechanism of bacterial tripartite efflux pumps

Neuberger

Luisi

2018

Research in Microbiology

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Efflux pumps are membrane proteins which contribute to multi-drug resistance. In Gram-negative bacteria, some of these pumps form complex tripartite assemblies in association with an outer membrane channel and a periplasmic membrane fusion protein. These tripartite machineries span both membranes and the periplasmic space, and they extrude from the bacterium chemically diverse toxic substrates. In this chapter, we summarise current understanding of the structural architecture, functionality, and regulation of tripartite multi-drug efflux assemblies.

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Control of RNA Stability by NrrF, an Iron-Regulated Small RNA in Neisseria gonorrhoeae

Cited by 23 publications

References 59 publications

Bacterial Adaptation to Antibiotics through Regulatory RNAs

Bacterial Adaptation to Antibiotics through Regulatory RNAs

Iron-regulated small RNA expression as Neisseria gonorrhoeae FA 1090 transitions into stationary phase growth

Structure and mechanism of bacterial tripartite efflux pumps

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