sRNA-controlled iron sparing response in Staphylococci
Open accessPublished version of a preprint
Abstract
Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.
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The isrR promoter contains two near consensus Fur box sequences.
“The isrR promoter contains two near consensus Fur box sequences (27).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
The Results section (“IsrR expression is repressed by the ferric uptake regulator Fur”; page not provided) identifies two predicted Fur boxes associated with isrR. It places only one within the promoter region; the second is immediately downstream of the transcriptional start site, so the claim that both are in the promoter overstates their location. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIsrR downregulates the expression of non-essential Fe utilizing genes including gltA, fdh, miaB and anaerobic nitrate respiration (nasD and narG).
“IsrR was demonstrated to downregulate the expression of non-essential Fe utilizing genes including gltA, fdh, miaB and anaerobic nitrate respiration (nasD and narG) (27,50).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
The Results sections on translational control and nitrate metabolism report that IsrR downregulates fdhA, nasD and narG reporter expression and inhibits nitrate reduction. But the paper identifies gltB2, not gltA, as the glutamate-synthase target, and our copy does not identify miaB as an IsrR target (searched: gltA, miaB). (LLM, conf=0.88)
Experimental — accuracy not yet measuredIsrR represses the expression of mRNA coding the Fe-requiring proteins AcnA, Sdh, GltB2, FdhA and MiaB.
“The results herein, in combination with previous findings, demonstrate that IsrR represses the expression of mRNA coding the Fe-requiring proteins AcnA, Sdh, GltB2, FdhA and MiaB (27,50).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
The Results (‘Translational control by IsrR’; page not supplied) show reduced expression of fdhA and gltB2 translation reporters. The bioinformatics Results list MiaB and CitB among predicted targets, and the Discussion identifies aconitase as acnA/citB, but these are not established there as repressed targets; the retrieved passages do not establish repression of Sdh. The paper also reports no significant effect of IsrR on fdhA or gltB2 mRNA stability, so its demonstrated repression concerns translation rather than mRNA abundance. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA recent publication demonstrated that the sRNA IsrR was required for growth during divalent metal starvation, suggesting that it is a functional analog of RyhB or FsrA.
“A recent publication demonstrated that the sRNA IsrR [originally named Tsr25 (26)] was required for growth during divalent metal starvation, suggesting that it is a functional analog of RyhB or FsrA (27).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
The Results section ('IsrR is an sRNA required for growth in iron-depleted media'; page unavailable) shows that IsrR is required for optimal S. aureus growth when iron is limited. The Discussion (page unavailable) describes shared iron-sparing targets with RyhB and FsrA, supporting the suggested functional analogy. The growth finding is specific to iron depletion, however, and does not establish a requirement during divalent-metal starvation generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe suppressor mutations correspond to a G→A change within the isrR sequence at the +1 position from the transcriptional start site as determined by RNA sequencing and at the +3 position as determined by 5′ RACE analysis.
“The mutations correspond to a G→A change within the isrR sequence at the +1 from the transcriptional start site as determined by RNA sequencing (47) and the +3 location as determined by 5′ Rapid Amplification of cDNA Ends (RACE) analysis (27).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
In Results, under “IsrR expression is repressed by the ferric uptake regulator Fur” (page unavailable), the paper reports that 5′/3′ RACE mapped the isrR transcription start to genomic position 1362894. It does not identify the cited G→A suppressor mutation or state that it lies at +3. The separate RNA-sequencing claim is attributed to citation (47), not this paper. (LLM, conf=0.83)
Experimental — accuracy not yet measured
An ΔisrR mutant caused decreased mortality in a murine septicemia model.
“Consistent with a role in pathogenesis, an ΔisrR mutant caused decreased mortality in a murine septicemia model (27).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
Fur is the dominant divalent metal-dependent transcriptional regulator controlling isrR transcription.
“These data are consistent with previous results demonstrating that isrR transcription is regulated by Fur (27) and suggest that Fur is the dominant divalent metal-dependent transcriptional regulator controlling isrR transcription.”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
IsrR is required for growth upon Fe depletion.
“This work also showed that IsrR is required for growth upon Fe depletion, leading to a model wherein IsrR contributes to Fe sparing upon Fur demetallation.”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
The chromosomal location of the suppressor mutation corresponds to tsr25 (recently renamed isrR), which codes for a sRNA.
“This chromosomal location corresponds to tsr25 (recently renamed isrR), which codes for a sRNA (26,27).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
IsrR has cytosine-rich regions (CRRs) that may be used to bind mRNA targets.
“Coronel-Tellez et al. determined that IsrR has CRRs, which may be used to bind mRNA targets (27).”
From The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence (2025) · cites this paper as [27]
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Cites
Enzymatic assembly of DNA molecules up to several hundred kilobases
Gibson, D. G., Young, L., Chuang, R.-Y., Venter, J. C., Hutchison, C. A., & Smith, H. O. (2009) · Nature Methods · doi:10.1038/nmeth.1318 · Cited by 9,742 · cited 1× · see citing works
“Plasmids were engineered by Gibson assembly (21) in Escherichia coli IM08B (22) as described (Supplementary Table S2), using the indicated appropriate primers (Supplementary Table S3) for PCR amplification.”
MethodTong, S. Y. C., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G. (2015) · Clinical Microbiology Reviews · doi:10.1128/cmr.00134-14 · Cited by 5,192 · cited 1× · see citing works
“Staphylococcus aureus is a human and animal opportunistic pathogen and a leading cause of nosocomial and community-acquired infections (16,17).”
BackgroundFIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247 · see citing works
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 1× · see citing works
“These products are provided to humans by nutrients and are also generated by the oxidation of endogenous NO synthase products (87,88).”
BackgroundNutritional immunity: transition metals at the pathogen–host interface
Hood, M. I., & Skaar, E. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2836 · Cited by 1,535 · see citing works
VARNA: Interactive drawing and editing of the RNA secondary structure
Darty, K., Denise, A., & Ponty, Y. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp250 · Cited by 1,375 · see citing works
Regulation by Small RNAs in Bacteria: Expanding Frontiers
Storz, G., Vogel, J., & Wassarman, K. M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.022 · Cited by 1,181 · cited 1× · see citing works
“aureus pathogenicity (46) and sRNAs are ubiquitous regulators for adaptation (47); we asked whether sRNAs are required in this bacterium to adapt to low iron availability, a condition encountered during infection.”
BackgroundMassé, E., & Gottesman, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032066599 · Cited by 1,154 · cited 1× · see citing works
“The mystery of this apparent paradox was solved by the discovery of a small regulatory RNA (sRNA) repressed by Fur, RyhB (8).”
BackgroundHfq and its constellation of RNA
Vogel, J., & Luisi, B. F. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2615 · Cited by 1,020 · cited 1× · see citing works
“In Enterobacteriaceae, Hfq is an RNA chaperone required for sRNA-mediated regulations (70).”
BackgroundOpening the Iron Box: Transcriptional Metalloregulation by the Fur Protein
Escolar, L., Pérez-Martín, J., & de Lorenzo, V. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.20.6223-6229.1999 · Cited by 815 · cited 1× · see citing works
“For many bacteria, the main contributor to iron homeostasis is the transcriptional regulator Fur (7).”
BackgroundThe Battle for Iron between Bacterial Pathogens and Their Vertebrate Hosts
Skaar, E. P. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000949 · Cited by 796 · see citing works
IntaRNA 2.0: enhanced and customizable prediction of RNA–RNA interactions
Mann, M., Wright, P. R., & Backofen, R. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx279 · Cited by 725 · see citing works
Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coliPreprint
Massé, É., Escorcia, F. E., & Gottesman, S. (2003) · Genes & Development · doi:10.1101/gad.1127103 · Cited by 705 · cited 1× · see citing works
“This classical approach should nevertheless be interpreted cautiously since i) stability of sRNA and mRNA targets depends on their base pairing and that ii) rifampicin prevents the synthesis of both partners, one of them being possibly limiting (68).”
BackgroundNutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701 · cited 1× · see citing works
“In parallel, pathogens have developed complex systems for iron assimilation leading to a “battle for iron” (1-4).”
BackgroundEffect of RyhB Small RNA on Global Iron Use in Escherichia coli
Massé, É., Vanderpool, C. K., & Gottesman, S. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.20.6962-6971.2005 · Cited by 550 · cited 1× · see citing works
“In low iron conditions, RyhB, assisted by the RNA chaperone Hfq, accumulates and pairs to mRNAs, preventing the expression of iron-containing proteins and inducing an iron-sparing response (9).”
BackgroundSmall RNAs in Bacteria and Archaea
Wagner, E. G. H., & Romby, P. (2015) · Advances in genetics · doi:10.1016/bs.adgen.2015.05.001 · Cited by 516 · cited 1× · see citing works
“Most trans-acting bacterial sRNAs are poorly conserved across species (52,53), including among the staphylococci (49,54).”
BackgroundTranscriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria
Troxell, B., & Hassan, H. M. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00059 · Cited by 500 · cited 1× · see citing works
“In parallel, pathogens have developed complex systems for iron assimilation leading to a “battle for iron” (1-4).”
BackgroundWilderman, P. J., Sowa, N. A., FitzGerald, D. J., FitzGerald, P. C., Gottesman, S., Ochsner, U. A., & Vasil, M. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403423101 · Cited by 455 · cited 1× · see citing works
“In Pseudomonas species, a major contributor to this adaptation is PrrF, a sRNA down-regulated by Fur contributing to iron homeostasis (11).”
BackgroundRegPrecise 3.0–a resource for genome-scale exploration of transcriptional regulation in bacteria
Novichkov, P. S., Kazakov, A. E., Ravcheev, D. A., Leyn, S. A., Kovaleva, G. Y., Sutormin, R. A., Kazanov, M. D., Riehl, W., Arkin, A. P., Dubchak, I., et al. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-745 · Cited by 451 · cited 3× · see citing works
“Fur boxes were detected using the motif finder FIMO (29) with isrR sequences retrieved from GLASSgo (option including 100nt upstream isrR sequences) and S. aureus NCTC8325 Fur consensus motifs from RegPrecise (30).”
BackgroundLocARNA-P: Accurate boundary prediction and improved detection of structural RNAs
Will, S., Joshi, T., Hofacker, I. L., Stadler, P. F., & Backofen, R. (2012) · RNA · doi:10.1261/rna.029041.111 · Cited by 396 · cited 5× · see citing works
“IsrR orthologs from different species of the Staphylococcus genus were used to feed LocARNA, a software for multiple alignments of RNAs that generates secondary structure predictions and highlights conserved pairing regions (31).”
MethodInfluentialHerbert, S., Ziebandt, A., Ohlsen, K., Schäfer, T., Hecker, M., Albrecht, D., Novick, R. P., & Götz, F. (2010) · Infection and Immunity · doi:10.1128/iai.00088-10 · Cited by 388 · cited 1× · see citing works
“Most of the work was performed with HG003, a Staphylococcus aureus model strain widely used for regulation studies (19).”
MethodHorsburgh, M. J., Clements, M. O., Crossley, H., Ingham, E., & Foster, S. J. (2001) · Infection and Immunity · doi:10.1128/iai.69.6.3744-3754.2001 · Cited by 365 · cited 1× · see citing works
“Chromosomal mutants (deletions and insertions) were either reported (25) or constructed for this study (Supplementary Table S1) using pIMAY derivatives as described (25), except for the fur::tet allele which was transferred from MJH010 (26) to HG003 and HG003 ΔisrR::tag135 by phage-mediated transduction.”
MethodCopraRNA and IntaRNA: predicting small RNA targets, networks and interaction domains
Wright, P. R., Georg, J., Mann, M., Sorescu, D. A., Richter, A. S., Lott, S. C., Kleinkauf, R., Hess, W. R., & Backofen, R. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku359 · Cited by 364 · cited 5× · see citing works
“Putative IsrR targets were found by CopraRNA (32) set with default parameters and isrR orthologs from S. aureus NCTC8325 (NC_007795), S. epidermidis RP62A (NC_002976), S. lugdunensis HKU09-01 (NC_013893), Staphylococcus pseudintermedius HKU10-03 (NC_014925), Staphylococcus pseudintermedius ED99 (NC_017568), Staphyloco…”
BackgroundMethodInfluentialBuilding Fe–S proteins: bacterial strategies
Py, B., & Barras, F. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2356 · Cited by 362 · cited 2× · see citing works
“aureus [Table S6, (33,34)], the probability of drawing n objects (23 best targets proposed by CopraRNA) and to have among k differentiated objects (mRNA expressing Fe–S containing proteins = 7) is given the following equation p (X = k) = Ck mC n−k N−m Cn N , where C represents a combination operator (https:”
BackgroundTranslational control and target recognition by Escherichia coli small RNAs in vivo
Urban, J. H., & Vogel, J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl1040 · Cited by 360 · see citing works
Anaerobic Gene Expression in Staphylococcus aureus
Fuchs, S., Pané‐Farré, J., Köhler, C., Hecker, M., & Engelmann, S. (2007) · Journal of Bacteriology · doi:10.1128/jb.00081-07 · Cited by 326 · see citing works
Horsburgh, M. J., Ingham, E., & Foster, S. J. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.2.468-475.2001 · Cited by 316 · see citing works
Nitrate and Nitrite in Health and Disease
Ma, L., Hu, L., Feng, X., & Wang, S. (2018) · Aging and disease · doi:10.14336/ad.2017.1207 · Cited by 294 · cited 1× · see citing works
“These products are provided to humans by nutrients and are also generated by the oxidation of endogenous NO synthase products (87,88).”
BackgroundSHAPE-directed RNA secondary structure prediction
Low, J., & Weeks, K. M. (2010) · Methods · doi:10.1016/j.ymeth.2010.06.007 · Cited by 291 · see citing works
Iron and infection: the heart of the matter
Bullen, J. J., Rogers, H. J., Spalding, P. B., & Ward, C. G. (2005) · FEMS Immunology & Medical Microbiology · doi:10.1016/j.femsim.2004.11.010 · Cited by 273 · see citing works
Staphylococcus aureus in Animals
Haag, A. F., Fitzgerald, J. R., & Penadés, J. R. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0060-2019 · Cited by 270 · cited 1× · see citing works
“Staphylococcus aureus is a human and animal opportunistic pathogen and a leading cause of nosocomial and community-acquired infections (16,17).”
BackgroundComparative genomics boosts target prediction for bacterial small RNAs
Wright, P. R., Richter, A. S., Papenfort, K., Mann, M., Vogel, J., Hess, W. R., Backofen, R., & Georg, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303248110 · Cited by 244 · cited 9× · see citing works
“Remarkably, nitrate reductase, nitrite reductase, glutamate synthase, formate dehydrogenase, aconitase, and hydratase methionine sulfoxide reductase, which are all putatively affected by IsrR (Supplementary Figure S4), also correspond to either putative or demonstrated enzymes affected by RyhB (5,64) suggesting a stri…”
BackgroundInfluentialGeissmann, T., Chevalier, C., Cros, M., Boisset, S., Fechter, P., Noirot, C., Schrenzel, J., François, P., Vandenesch, F., Gaspin, C., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp668 · Cited by 242 · see citing works
Complete Bypass of Restriction Systems for Major Staphylococcus aureus Lineages
Monk, I. R., Tree, J. J., Howden, B. P., Stinear, T. P., & Foster, T. J. (2015) · mBio · doi:10.1128/mbio.00308-15 · Cited by 242 · see citing works
Genome-Wide Identification of Regulatory RNAs in the Human Pathogen Clostridium difficile
Soutourina, O. A., Monot, M., Boudry, P., Saujet, L., Pichon, C., Sismeiro, O., Semenova, E., Severinov, K., Bouguénec, C. L., Coppée, J., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003493 · Cited by 238 · cited 1× · see citing works
“5’/3’ RACE was performed as previously described (37) with some modifications.”
MethodGaballa, A., Antelmann, H., Aguilar, C., Khakh, S. K., Song, K.-B., Smaldone, G. T., & Helmann, J. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711752105 · Cited by 232 · cited 1× · see citing works
“FsrA, but not the other sRNAs, binds to the Shine-Dalgarno sequence via a C-rich motif (96), but requires three chaperone functions.”
BackgroundGlobal Changes in Staphylococcus aureus Gene Expression in Human Blood
Małachowa, N., Whitney, A. R., Kobayashi, S. D., Sturdevant, D. E., Kennedy, A. D., Braughton, K. R., Shabb, D. W., Diep, B. A., Chambers, H. F. “., Otto, M. J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018617 · Cited by 226 · cited 1× · see citing works
“Environments that failed to provide free iron, such as serum, promoted the induction of iron-repressed genes in infecting bacteria (80,81).”
BackgroundIron acquisition strategies of bacterial pathogens
Sheldon, J. R., Laakso, H. A., & Heinrichs, D. E. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0010-2015 · Cited by 219 · cited 1× · see citing works
“In parallel, pathogens have developed complex systems for iron assimilation leading to a “battle for iron” (1-4).”
BackgroundKarabiber, F., McGinnis, J. L., Favorov, O. V., & Weeks, K. M. (2012) · RNA · doi:10.1261/rna.036327.112 · Cited by 218 · cited 2× · see citing works
“The resulting traces were analyzed using QuSHAPE (43).”
MethodStaphylococcus aureus Transcriptome Architecture: From Laboratory to Infection-Mimicking Conditions
Mäder, U., Nicolas, P., Depke, M., Pané‐Farré, J., Débarbouillé, M., van der Kooi‐Pol, M. M., Guérin, C., Dérozier, S., Hiron, A., Jarmer, H. Ø., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005962 · Cited by 203 · cited 6× · see citing works
“The deletion associated with tag135 inactivated an sRNA reported in two global studies under the names S596 (50) and Tsr25 (51).”
BackgroundInfluentialBohn, C., Rigoulay, C., Chabelskaya, S. V., Sharma, C. M., Marchais, A., Skorski, P., Borezée‐Durant, E., Barbet, R., Jacquet, E., Jacq, A., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq462 · Cited by 200 · cited 2× · see citing works
“This less-common interspecies conservation (another example in S. aureus is RsaE (95)) reveals a selective pressure to maintain IsrR sequence, structure, and regulation intact.”
BackgroundSelf-citationBenito, Y., Kolb, F. A., Romby, P., Lina, G., Étienne, J., & Vandenesch, F. (2000) · RNA · doi:10.1017/s1355838200992550 · Cited by 199 · see citing works
No detectable effect of RNA-binding protein Hfq absence in Staphylococcus aureus
Bohn, C., Rigoulay, C., & Bouloc, P. (2007) · BMC Microbiology · doi:10.1186/1471-2180-7-10 · Cited by 191 · see citing works
Self-citationMouse models for infectious diseases caused by Staphylococcus aureus
Kim, H. K., Missiakas, D. M., & Schneewind, O. (2014) · Journal of Immunological Methods · doi:10.1016/j.jim.2014.04.007 · Cited by 180 · cited 1× · see citing works
“We compared the virulence of ΔisrR, ΔisrR locus2::isrR + and parental (HG003) strains injected intravenously in a mouse septicemia model (78).”
MethodTorres, V. J., Attia, A. S., Mason, W. J., Hood, M. I., Corbin, B. D., Beasley, F. C., Anderson, K. L., Stauff, D. L., McDonald, W. H., Zimmerman, L. J., et al. (2010) · Infection and Immunity · doi:10.1128/iai.01423-09 · Cited by 169 · cited 1× · see citing works
“Inactivation of the Fur repressor leads to downregulation of numerous genes (83,84).”
BackgroundA battle for iron: host sequestration and Staphylococcus aureus acquisition
Haley, K. P., & Skaar, E. P. (2012) · Microbes and Infection · doi:10.1016/j.micinf.2011.11.001 · Cited by 157 · cited 1× · see citing works
“aureus pathogenicity (46) and sRNAs are ubiquitous regulators for adaptation (47); we asked whether sRNAs are required in this bacterium to adapt to low iron availability, a condition encountered during infection.”
BackgroundExpression of Virulence Factors by Staphylococcus aureus Grown in Serum
Oogai, Y., Matsuo, M., Hashimoto, M., Kato, F., Sugai, M., & Komatsuzawa, H. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.05316-11 · Cited by 155 · cited 1× · see citing works
“Environments that failed to provide free iron, such as serum, promoted the induction of iron-repressed genes in infecting bacteria (80,81).”
BackgroundAureo Wiki The repository of the Staphylococcus aureus research and annotation community
Fuchs, S., Mehlan, H., Bernhardt, J., Hennig, A., Michalik, S., Surmann, K., Pané‐Farré, J., Giese, A., Weiß, S., Backert, L., et al. (2017) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2017.11.011 · Cited by 147 · cited 1× · see citing works
“1) retrieved from Genbank and Aureowiki (20).”
Bacterial Iron Homeostasis Regulation by sRNAs
Chareyre, S., & Mandin, P. (2018) · Microbiology Spectrum · doi:10.1128/microbiolspec.rwr-0010-2017 · Cited by 125 · cited 12× · see citing works
“Remarkably, nitrate reductase, nitrite reductase, glutamate synthase, formate dehydrogenase, aconitase, and hydratase methionine sulfoxide reductase, which are all putatively affected by IsrR (Supplementary Figure S4), also correspond to either putative or demonstrated enzymes affected by RyhB (5,64) suggesting a stri…”
BackgroundInfluentialLalaouna, D., Baude, J., Wu, Z., Tomasini, A., Chicher, J., Marzi, S., Vandenesch, F., Romby, P., Caldelari, I., & Moreau, K. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz728 · Cited by 114 · cited 1× · see citing works
“aureus sRNA produced in response to manganese (Mn) starvation that inhibits the synthesis of the superoxide dismutase SodA, a Mn-containing enzyme (82).”
BackgroundIron-responsive bacterial small RNAs: variations on a theme
Oglesby-Sherrouse, A. G., & Murphy, E. R. (2013) · Metallomics · doi:10.1039/c3mt20224k · Cited by 112 · cited 1× · see citing works
“RyhB orthologs are present in many species from the Enterobacteriaceae family where they contribute to adaptation to low iron conditions (5,10).”
BackgroundPi, H., & Helmann, J. D. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713008114 · Cited by 109 · cited 1× · see citing works
“In Bacillus subtilis, FsrA sRNA is down-regulated by Fur, and with the help of three RNA chaperones, FbpABC, it prevents the expression of iron-containing enzymes (12-14).”
BackgroundCharacterization of the Oxygen-Responsive NreABC Regulon of Staphylococcus aureus
Schlag, S., Fuchs, S., Nerz, C., Gaupp, R., Engelmann, S., Liebeke, M., Lalk, M., Hecker, M., & Götz, F. (2008) · Journal of Bacteriology · doi:10.1128/jb.00905-08 · Cited by 108 · cited 1× · see citing works
“Other putative targets, such as moaD and nreC mRNAs, are also associated with Fe-S containing complexes (62,63).”
BackgroundOn the facultative requirement of the bacterial RNA chaperone, Hfq
Jousselin, A., Metzinger, L., & Felden, B. (2009) · Trends in Microbiology · doi:10.1016/j.tim.2009.06.003 · Cited by 99 · see citing works
Self-citationMarchetti, M., Bei, O. D., Bettati, S., Campanini, B., Kovachka, S., Gianquinto, E., Spyrakis, F., & Ronda, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062145 · Cited by 92 · cited 1× · see citing works
“aureus pathogenicity and its iron status is established (79).”
BackgroundTranscriptional and Post-transcriptional Control of the Nitrate Respiration in Bacteria
Durand, S., & Guillier, M. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.667758 · Cited by 91 · cited 2× · see citing works
“Biocomputing analysis (Supplementary Figure S4) suggests that IsrR targets nreC mRNA; If so, the expression of the nitrogen respiration pathway would be simultaneously downregulated by targeting mRNAs encoding dissimilatory nitrate reduction enzymes and their transcriptional activator. sRNAs that directly affect nitro…”
BackgroundAn assessment of bacterial small RNA target prediction programs
Pain, A., Ott, A., Amine, H., Rochat, T., Bouloc, P., & Gautheret, D. (2015) · RNA Biology · doi:10.1080/15476286.2015.1020269 · Cited by 90 · cited 2× · see citing works
“As trans-acting bacterial sRNAs base-pair to RNAs, it is possible to predict their putative targets by bioinformatics; however, some predictive programs generate false positive candidates (61).”
BackgroundSelf-citationComparison of nitrate reductase mutants of Escherichia coli selected by alternative procedures
Glaser, J. H., & DeMoss, J. A. (1972) · Molecular and General Genetics MGG · doi:10.1007/bf00334254 · Cited by 90 · cited 1× · see citing works
“20 (67), suggesting that FdhF is associated with the nitrate dissimilatory pathway.”
BackgroundWang, H., & Gunsalus, R. P. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.17.5076-5085.2003 · Cited by 89 · cited 1× · see citing works
“coli, the fdhF gene encoding a molybdenum-dependent formate dehydrogenase is regulated by nitrate (66).”
BackgroundSmaldone, G. T., Revelles, O., Gaballa, A., Sauer, U., Antelmann, H., & Helmann, J. D. (2012) · Journal of Bacteriology · doi:10.1128/jb.05990-11 · Cited by 87 · cited 1× · see citing works
“In Bacillus subtilis, FsrA sRNA is down-regulated by Fur, and with the help of three RNA chaperones, FbpABC, it prevents the expression of iron-containing enzymes (12-14).”
BackgroundSRD: a Staphylococcus regulatory RNA database
Sassi, M., Augagneur, Y., Mauro, T., Ivain, L., Chabelskaya, S. V., Hallier, M., Sallou, O., & Felden, B. (2015) · RNA · doi:10.1261/rna.049346.114 · Cited by 86 · see citing works
Self-citationMarchais, A., Naville, M., Bohn, C., Bouloc, P., & Gautheret, D. (2009) · Genome Research · doi:10.1101/gr.089714.108 · Cited by 85 · cited 2× · see citing works
“RNA was extracted as described (27) and Northern blots were performed as described above.”
MethodSelf-citationGerrick, E. R., Barbier, T., Chase, M. R., Xu, R. F., François, J., Lin, V. H., Szucs, M. J., Rock, J. M., Ahmad, R., Tjaden, B. C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718003115 · Cited by 84 · cited 8× · see citing works
“As with the parental strain (Figure 7 and Supplementary Figure S10), the reporter fusions were downregulated by IsrR despite the absence of Hfq (Supplementary Figure S11A).”
BackgroundInfluentialCarroll, R. K., Weiss, A., Broach, W. H., Wiemels, R. E., Mogen, A. B., Rice, K. C., & Shaw, L. N. (2016) · mBio · doi:10.1128/mbio.01990-15 · Cited by 76 · cited 3× · see citing works
“RsaOG, RsaG, Teg16, SsrS and RsaD sRNAs were reported as upregulated in serum (51), but they do not contribute to S.”
BackgroundAllard, M., Moisan, H., Brouillette, É., Gervais, A. L., Jacques, M., Lacasse, P., Diarra, M. S., & Malouin, F. (2006) · Microbes and Infection · doi:10.1016/j.micinf.2006.01.022 · Cited by 67 · cited 1× · see citing works
“aureus (85) are IsrR targets predicted by Copra RNA, including narG and nasD.”
BackgroundNitrate reductase system in Staphylococcus aureus wild type and mutants
Burke, K. A., & Lascelles, J. (1975) · Journal of Bacteriology · doi:10.1128/jb.123.1.308-316.1975 · Cited by 66 · cited 1× · see citing works
“In the absence of oxygen, Staphylococci use nitrate and nitrite as electron acceptors of the anaerobic respiratory chain (86).”
BackgroundThe NreA Protein Functions as a Nitrate Receptor in the Staphylococcal Nitrate Regulation System
Niemann, V., Koch‐Singenstreu, M., Neu, A., Nilkens, S., Götz, F., Unden, G., & Stehle, T. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.12.026 · Cited by 63 · cited 2× · see citing works
“Transcription of nar and nas operons depends on the NreABC regulatory system, whose activity requires the presence of nitrate and the absence of oxygen (63).”
BackgroundKamps, A., Achebach, S., Fedtke, I., Unden, G., & Götz, F. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04024.x · Cited by 63 · see citing works
Genetic Regulation of Metal Ion Homeostasis in Staphylococcus aureus
Price, E. E., & Boyd, J. M. (2020) · Trends in Microbiology · doi:10.1016/j.tim.2020.04.004 · Cited by 59 · cited 1× · see citing works
“Indeed, iron limitation in the host is counteracted by alleviation of Fur repression, leading to the production of iron-scavenging siderophores (18).”
BackgroundTracking the Elusive Function of Bacillus subtilis Hfq
Rochat, T., Delumeau, O., Figueroa‐Bossi, N., Noirot, P. H., Bossi, L., Dervyn, E., & Bouloc, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124977 · Cited by 58 · see citing works
Self-citationOrigin, Evolution, and Loss of Bacterial Small RNAs
Dutcher, H. A., & Raghavan, R. (2018) · Microbiology Spectrum · doi:10.1128/microbiolspec.rwr-0004-2017 · Cited by 57 · cited 1× · see citing works
“Most trans-acting bacterial sRNAs are poorly conserved across species (52,53), including among the staphylococci (49,54).”
BackgroundAssessment of Bona Fide sRNAs in Staphylococcus aureus
Liu, W., Rochat, T., Toffano‐Nioche, C., Lam, T. N. L., Bouloc, P., & Morvan, C. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00228 · Cited by 54 · cited 5× · see citing works
“We therefore restricted our collection to 48 mutants corresponding to nearly all known HG003 “bona fide sRNAs”, defined as those that are genetically independent with their own promoter and terminator (49).”
BackgroundInfluentialSelf-citationRochat, T., Bohn, C., Morvan, C., Lam, T. N. L., Razvi, F., Pain, A., Toffano‐Nioche, C., Ponien, P., Jacq, A., Jacquet, E., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky584 · Cited by 54 · see citing works
Self-citationFresh layers of RNA-mediated regulation in Gram-positive bacteria
Bouloc, P., & Repoila, F. (2016) · Current Opinion in Microbiology · doi:10.1016/j.mib.2015.12.008 · Cited by 51 · see citing works
Self-citationGLASSgo – Automated and Reliable Detection of sRNA Homologs From a Single Input Sequence
Lott, S. C., Schäfer, R. A., Mann, M., Backofen, R., Hess, W. R., Voß, B., & Georg, J. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00124 · Cited by 50 · cited 4× · see citing works
“The alignment was obtained using LocARNA (31) with isrR sequences from indicated strains generated by GLASSgo (28) as inputs.”
MethodInfluentialImpact of Hfq on the Bacillus subtilis Transcriptome
Hämmerle, H., Amman, F., Večerek, B., Stülke, J., Hofacker, I. L., & Bläsi, U. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098661 · Cited by 47 · see citing works
Two ribosome recruitment sites direct multiple translation events within HIV1 Gag open reading frame
Deforges, J., de Breyne, S., Ameur, M., Ulryck, N., Chamond, N., Saaidi, A., Ponty, Y., Ohlmann, T., & Sargueil, B. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx303 · Cited by 44 · cited 1× · see citing works
“RNAs were probed in the presence and absence of 5 mM Mg2+ using methyl-7-nitroisatoic anhydride (1M7) and modifications were revealed by selective 2’-hydroxyl acylation and analyzed by primer extension (SHAPE) as described (41,42) with slight modifications.”
MethodSelf-citationMulti-metal nutrient restriction and crosstalk in metallostasis systems in microbial pathogens
Jordan, M. R., Wang, J., Capdevila, D. A., & Giedroc, D. P. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.01.010 · Cited by 44 · cited 1× · see citing works
“Since most living organisms need iron but are sensitive to its excess, strict regulation of iron uptake and iron-containing enzymes is necessary (5,6).”
BackgroundDispensable PDZ domain of Escherichia coli YaeL essential protease
Bohn, C., Collier, J., & Bouloc, P. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.03985.x · Cited by 43 · cited 3× · see citing works
“Plasmids expressing sGFP were constructed in MG1655Z1 pcnB::Km, a strain that decreases ColE1 plasmid copy number and therefore reduces toxic effects produced by high amounts of certain proteins in E. coli.”
BackgroundSelf-citationGaballa, A., & Helmann, J. D. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05905.x · Cited by 40 · cited 1× · see citing works
“In Bacillus subtilis, FsrA sRNA is down-regulated by Fur, and with the help of three RNA chaperones, FbpABC, it prevents the expression of iron-containing enzymes (12-14).”
BackgroundIvain, L., Bordeau, V., Eyraud, A., Hallier, M., Dréano, S., Tattevin, P., Felden, B., & Chabelskaya, S. V. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx190 · Cited by 38 · cited 1× · see citing works
“The principle of a reporter assay for sRNA activity was described for Enterobacteria (38) and Gram-positive bacteria (39).”
BackgroundSelf-citationRegulatory RNA at the crossroads of carbon and nitrogen metabolism in photosynthetic cyanobacteria
Muro-Pastor, A. M., & Hess, W. R. (2019) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2019.194477 · Cited by 37 · cited 1× · see citing works
“RNAs responsive to Fe (rrF) are indeed common in bacteria (5,93).”
BackgroundZupok, A., Iobbi‐Nivol, C., Méjean, V., & Leimkühler, S. (2019) · Metallomics · doi:10.1039/c9mt00186g · Cited by 36 · cited 1× · see citing works
“Other putative targets, such as moaD and nreC mRNAs, are also associated with Fe-S containing complexes (62,63).”
BackgroundCloing and characterization of an Escherichia coli gene, pcnB, affecting plasmid copy number
March, J. B., Colloms, M. D., Hart-Davis, D., Oliver, I. R., & Masters, M. (1989) · Molecular Microbiology · doi:10.1111/j.1365-2958.1989.tb00239.x · Cited by 35 · cited 1× · see citing works
“MG1655Z1 pcnB::Km was constructed by the introduction of the pcnB::Km allele (23) in MG1655Z1 (24) by P1-mediated transduction.”
BackgroundA small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity
Huyen, K. B. L., Gonzalez, C. D., Pascreau, G., Bordeau, V., Cattoir, V., Liu, W., Bouloc, P., Felden, B., & Chabelskaya, S. V. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab782 · Cited by 35 · cited 1× · see citing works
“Gel-shift assays were performed as described (35) with the following modifications: RNAs were denaturated in 50 mM Tris pH”
MethodSelf-citationLack of interchangeability of Hfq-like proteins
Rochat, T., Bouloc, P., Yang, Q., Bossi, L., & Figueroa‐Bossi, N. (2012) · Biochimie · doi:10.1016/j.biochi.2012.01.016 · Cited by 34 · see citing works
Self-citationNitrate/oxygen co‐sensing by an NreA / NreB sensor complex of S taphylococcus carnosus
Nilkens, S., Koch‐Singenstreu, M., Niemann, V., Götz, F., Stehle, T., & Unden, G. (2013) · Molecular Microbiology · doi:10.1111/mmi.12464 · Cited by 34 · cited 2× · see citing works
“Transcription of nar and nas operons depends on the NreABC regulatory system, whose activity requires the presence of nitrate and the absence of oxygen (63).”
BackgroundSmall RNAs Involved in Regulation of Nitrogen Metabolism
Prasse, D., & Schmitz, R. A. (2018) · Microbiology Spectrum · doi:10.1128/microbiolspec.rwr-0018-2018 · Cited by 30 · cited 2× · see citing works
“Biocomputing analysis (Supplementary Figure S4) suggests that IsrR targets nreC mRNA; If so, the expression of the nitrogen respiration pathway would be simultaneously downregulated by targeting mRNAs encoding dissimilatory nitrate reduction enzymes and their transcriptional activator. sRNAs that directly affect nitro…”
BackgroundDeforges, J., Chamond, N., & Sargueil, B. (2012) · Biochimie · doi:10.1016/j.biochi.2012.02.009 · Cited by 29 · cited 1× · see citing works
“9 RNAs were probed in the presence and absence of 5 mM Mg 2+ using methyl-7-nitroisatoic anhydride (1M7) and modifications were revealed by selective 2’-hydroxyl acylation and analyzed by primer extension (SHAPE) as described (41,42) with slight modifications.”
MethodSelf-citationFrezza, E., Courban, A., Allouche, D., Sargueil, B., & Pasquali, S. (2019) · Methods · doi:10.1016/j.ymeth.2019.05.021 · Cited by 27 · cited 1× · see citing works
“RNAs were incubated with 1-Methyl-7-nitroisatoic anhydride (1M7), which specifically reacts with flexible nucleotides (58,59).”
MethodSelf-citationStaphylococcus aureus pigmentation is not controlled by Hfq
Liu, W., Boudry, P., Bohn, C., & Bouloc, P. (2020) · BMC Research Notes · doi:10.1186/s13104-020-4934-4 · Cited by 24 · cited 1× · see citing works
“Fluorescent tests to evaluate the contribution of Fur boxes were performed with 8325-4, a ‘pigment-less’ strain (36) containing either pPisrR::gfp, pPisrR1::gfp, pPisrR2::gfp or pPisrR1&2::gfp (Supplementary Table S2).”
MethodSelf-citationFinding sRNA-associated phenotypes by competition assays: An example with Staphylococcus aureus
Lam, T. N. L., Morvan, C., Liu, W., Bohn, C., Jaszczyszyn, Y., & Bouloc, P. (2016) · Methods · doi:10.1016/j.ymeth.2016.11.018 · Cited by 22 · cited 5× · see citing works
“DNA-seq data from fitness experiments were analyzed using a reported pipeline (25).”
MethodInfluentialSelf-citationIPANEMAP: integrative probing analysis of nucleic acids empowered by multiple accessibility profiles
Saaidi, A., Allouche, D., Régnier, M., Sargueil, B., & Ponty, Y. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa607 · Cited by 20 · cited 7× · see citing works
“IsrR secondary structure model obtained using IPANEMAP IsrR was probed with 1M7 at 37°C in 40 mM HEPES pH 7.5, 150 mM KCl with/without 5 mM MgCl2.”
MethodInfluentialSelf-citationProgress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
Bisschop, G. D., Allouche, D., Frezza, E., Masquida, B., Ponty, Y., Will, S., & Sargueil, B. (2021) · Non-Coding RNA · doi:10.3390/ncrna7040071 · Cited by 14 · cited 1× · see citing works
“Only a few significant local reactivity changes located after CCR1 stem-loop were observed suggesting that this region of IsrR does not adopt an extensive tertiary structure (60).”
BackgroundSelf-citation6S RNA-Dependent Susceptibility to RNA Polymerase Inhibitors
Esberard, M., Hallier, M., Liu, W., Morvan, C., Bossi, L., Figueroa‐Bossi, N., Felden, B., & Bouloc, P. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02435-21 · Cited by 10 · cited 1× · see citing works
“To address this question, we took advantage of a strategy that we recently developed, based on a competitive fitness evaluation of sRNA mutant libraries (25,48).”
MethodSelf-citationRNA Footprinting Using Small Chemical Reagents
Bisschop, G. D., & Sargueil, B. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1499-0_2 · Cited by 8 · cited 2× · see citing works
“Probing profiles were compared as described (40).”
MethodSelf-citationDuverger, Y., & Py, B. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1605-5_1 · Cited by 4 · cited 2× · see citing works
“aureus [Table S6, (33,34)], the probability of drawing n objects (23 best targets proposed by CopraRNA) and to have among k differentiated objects (mRNA expressing Fe–S containing proteins = 7) is given the following equation p (X = k) = Ck mC n−k N−m Cn N , where C represents a combination operator (https:”
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Ganske, A., Busch, L. M., Hentschker, C., Reder, A., Michalik, S., Surmann, K., Völker, U., & Mäder, U. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1439352 · Cited by 24 · see citing works
Barrault, M., Chabelskaya, S., Coronel-Tellez, R. H., Toffano-Nioche, C., Jacquet, E., & Bouloc, P. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae506 · Cited by 20 · see citing works
Ding, X., Masselot, C. R., Fu, X., Léonard, R., Marsac, B., Dauriat, C. J. G., Lepissier, A., Rytter, H., Ramond, E. J., Dupuis, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43863-2 · Cited by 20 · see citing works
The <i>Staphylococcus aureus</i> non-coding RNA IsrR regulates TCA cycle activity and virulence
Rios-Delgado, G., McReynolds, A. K. G., Pagella, E. A., Norambuena, J., Briaud, P., Zheng, V., Munneke, M. J., Kim, J., Racine, H., Carroll, R. K., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkae1243 · Cited by 19 · see citing works
Coordinated adaptation of Staphylococcus aureus to calprotectin-dependent metal sequestration
Ruiz, V. M. R., Freiberg, J. A., Weiss, A., Green, E. R., Jobson, M.-E., Felton, E. A., Shaw, L. N., Chazin, W., & Skaar, E. P. (2024) · mBio · doi:10.1128/mbio.01389-24 · Cited by 18 · see citing works
Boyd, J. M., Ryan Kaler, K., Esquilín-Lebrón, K., Pall, A., Campbell, C. J., Foley, M. E., Rios-Delgado, G., Mustor, E. M., Stephens, T. G., Bovermann, H., et al. (2024) · mBio · doi:10.1128/mbio.02310-24 · Cited by 14 · see citing works
“We and others recently discovered a Fur-regulated sRNA in S. aureus called IsrR that decreases the expression of specific Fe-requiring proteins or processes to spare Fe ions for essential metabolic processes (15–17).”
Banerjee, R. (2025) · Non-Coding RNA · doi:10.3390/ncrna11030036 · Cited by 13 · see citing works
“Interestingly, Coronel-Tellez et al. identified the small RNA IsrR that provides an iron-sparing response in Staphylococcus sp. akin to RyhB [143].”
Yue, Z., Liu, Y., Chen, Y., Chen, C., Zhang, J., He, L., & Ma, K. (2023) · Microorganisms · doi:10.3390/microorganisms11020367 · Cited by 11 · see citing works
Zeng, S., Shi, Q., Liu, Y., Li, M., Li, M., Zhang, S., Li, Q., Pu, J., Shen, C., Huang, B., et al. (2023) · Microbial Pathogenesis · doi:10.1016/j.micpath.2023.106124 · Cited by 11 · see citing works
Barrault, M., Leclair, E., Kumeko, E. K., Jacquet, E., & Bouloc, P. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.03888-23 · Cited by 11 · see citing works
Self-citationHa, K. P., Kumeko, E. K., & Bouloc, P. (2025) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01176-24 · Cited by 10 · see citing works
Self-citationInsights into the regulatory role of bacterial sncRNA and its extracellular delivery via OMVs
He, M., Yin, S., Huang, X., Li, Y., Li, B., Gong, T., & Liu, Q. (2023) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12855-z · Cited by 10 · see citing works
“Numerous studies have demonstrated that sncRNAs are key regulators of iron homeostasis in bacteria (Chareyre and Mandin 2018; Coronel-Tellez et al. 2022).”
Busch, L. M., Ganske, A., Reißel, S., Bleul, L., Hentschker, C., Wolfgramm, H., Steil, L., Salazar, M. G., Schaffer, M., Reder, A., et al. (2025) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5c00059 · Cited by 9 · see citing works
“19 Coronel-Tellez et al. (2022) 18 and Rios-Delgado et al. (2025) 23 demonstrated the relevance of IsrR for S. aureus pathogenicity in mice.”
Flores, E. S., Jagodnik, J., Quenette, F., Korepanov, A. P., & Guillier, M. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1131 · Cited by 8 · see citing works
Rios-Delgado, G., McFarlane, R. A., Zheng, V., Kim, J., Parker, D., Kehl‐Fie, T. E., Lalaouna, D., & Boyd, J. M. (2025) · mBio · doi:10.1128/mbio.01415-25 · Cited by 7 · see citing works
The Staphylococcus aureus small non-coding RNA IsrR regulates TCA cycle activity and virulencePreprint
Rios-Delgado, G., McReynolds, A. K. G., Pagella, E. A., Norambuena, J., Briaud, P., Zheng, V., Munneke, M. J., Kim, J., Racine, H., Carroll, R. K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.03.601953 · Cited by 6 · see citing works
“The mutations correspond to a G à A change within the isrR sequence at the +1 location as determined by RNA sequencing (45) and the +3 location as determined by 5’ RACE analysis (25).”
InfluentialUnusual Relationship between Iron Deprivation and Organophosphate Hydrolase Expression
Nandavaram, A., Nandakumar, A., Kashif, G. M., Sagar, A. L., Shailaja, G., Ramesh, A., & Siddavattam, D. (2023) · Applied and Environmental Microbiology · doi:10.1128/aem.01903-22 · Cited by 5 · see citing works
SSR42 is a novel regulator of cytolytic activity in Staphylococcus aureus
Jobson, M.-E., Tomlinson, B. R., Mustor, E. M., Felton, E. A., Weiss, A., Caswell, C. C., & Shaw, L. N. (2025) · mBio · doi:10.1128/mbio.00772-25 · Cited by 4 · see citing works
Boyd, J. M., Esquilín-Lebrón, K., Campbell, C. J., Kaler, K. R., Norambuena, J., Foley, M. E., Stephens, T. G., Rios, G., Mereddy, G., Zheng, V., et al. (2023) · doi:10.1101/2023.10.03.560778 · Cited by 4 · see citing works
“98 aureus) that helps to optimize Fe usage (12).”
BackgroundRios-Delgado, G., & Boyd, J. M. (2026) · mBio · doi:10.1128/mbio.01110-26 · Cited by 3 · see citing works
“It contains three conserved cytosine-rich regions (CRRs), each located within unpaired single-stranded regions within its secondary structure (78).”
InfluentialMcFarlane, R. A., Radin, J. N., Mazgaj, R., Waldron, K. J., Lalaouna, D., & Kehl‐Fie, T. E. (2025) · mBio · doi:10.1128/mbio.01439-25 · Cited by 3 · see citing works
“However, it is now apparent that post-transcriptional regulation contrib utes to controlling the bacterial response to iron (Fe) availability, through the small RNA (sRNA) RyhB and analogs, enabling adaptation to Fe-limited environments (18–21).”
New RoxS sRNA Targets Identified in Bacillus subtilis by Pulsed SILAC
Allouche, D., Kostova, G., Hamon, M., Marchand, C. H., Caron, M., Belhocine, S., Christol, N., Charteau, V., Condon, C., & Durand, S. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.00471-23 · Cited by 3 · see citing works
“A recent study in Staphylococcus aureus identified two targets of the IsrR RNA, induced during iron starvation, that are primarily affected at the translational level (9).”
BackgroundIPANEMAP Suite: a pipeline for probing-informed RNA structure modeling.
Hardouin, P., Pan, N., du Moutier, F.-X. L., Chamond, N., Ponty, Y., Will, S., & Sargueil, B. (2025) · PubMed Central · doi:10.1093/nargab/lqaf028 · Cited by 3 · see citing works
“RNA structure probing was carried out as previously described in [ 32 , 33 ].”
Self-citationGonzález-Espinoza, G., Prévost, K., Hussain, F., Radin, J. N., Valle, C. D. V., Maucotel, J., Barroso, M. V., Marteyn, B., Massé, É., Romby, P., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.30.615890 · Cited by 3 · see citing works
“Notably, this putative target was not evidenced by prior studies 22,25,38 .”
BackgroundFermentative growth decreases the iron demand of Staphylococcus aureus
Boyd, J. M., Rios-Delgado, G., Esquilín-Lebrón, K., Kaler, K. R., Mereddy, G., Norambuena, J., Zheng, V., Beavers, W. N., Kim, J., Parker, D., et al. (2025) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2025.113085 · Cited by 2 · see citing works
Liang, Z., Wang, S., Zhu, X., Ma, J., Yao, H., & Wu, Z. (2025) · Virulence · doi:10.1080/21505594.2025.2491635 · Cited by 1 · see citing works
“Recent studies have highlighted the critical role of small RNAs (sRNA) as virulence regulators in pathogenic bacteria [9]. sRNAs play critical roles in adapting to complex stress conditions, such as nutrient availability [10], oxidative stress [11], and iron star-vation [12].”
Ortíz-Severín, J., Geoffroy, P., Aravena, P., Christian Hodar, Q., Palma, D. E., González, M., & Cambiazo, V. (2025) · Applied and Environmental Microbiology · doi:10.1128/aem.01560-25 · Cited by 1 · see citing works
The Small Noncoding RNA, RsaC, Is Essential for Staphylococcus a ureus Virulence
Panthee, S., Paudel, A., Ohgi, S., Sekimizu, K., & Hamamoto, H. (2026) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiag282 · Cited by 1 · see citing works
A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus
Charbonnier, M., Racine, H., Probst-Lotze, S., Radin, J. N., Rios-Delgado, G., Lyu, L., Laster, H. M., Kohl, M. P., Mazgaj, R., Marion, B., et al. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkag894 · Cited by 1 · see citing works
“In S. aureus , Fe, Mn, and Zn homeostasis are all controlled by a tandem of transcription factor and sRNA: Fur-IsrR [ 29 , 30 ], MntR-RsaC [ 28 ], and Zur-ZinS.”
Bronsard, J., Silard, C., Legros, J., Germain‐Amiot, N., Hallier, M., & Augagneur, Y. (2025) · BMC Microbiology · doi:10.1186/s12866-025-04113-1 · Cited by 1 · see citing works
A type I 3’ UTR-derived sRNA is involved in heme metabolism and virulence in Staphylococcus aureusPreprint
Silard, C., Germain‐Amiot, N., Poirette, P., Legros, J., Durao, G., Martinais, S., Mirouze, N., & Augagneur, Y. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.25.620293 · Cited by 2 · see citing works
“Additionally, complementation of the Δsrn_9342 mutant with its promoter at a neutral genomic locus (SAPhB1508) [34], fully restored the parental Srn_9342 S/L pattern of expression ( Fig.”
BackgroundMethodInfluentialAn RNA regulates iron homeostasis and host mucus colonization in Bacteroides thetaiotaomicronPreprint
Prezza, G., Fansler, R. T., Guest, T., Mädler, G., Schlauch, H., Zhu, W., & Westermann, A. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.08.672848 · Cited by 1 · see citing works
New RoxS sRNA targets identified in B. subtilis by pulsed SILACPreprint
Allouche, D., Kostova, G., Hamon, M., Marchand, C. H., Caron, M., Belhocine, S., Christol, N., Charteau, V., Condon, C., & Durand, S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.17.528916
“of the IsrR RNA, induced during iron starvation, that are primarily affected at the 18 translational level (7).”
BackgroundOstyn, E., Hallier, M., Dréano, S., Augagneur, Y., & Pinel‐Marie, M. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4812519
FabF and FadM Cooperate to Recycle Fatty Acids and Rescue Δ plsX Lethality in Staphylococcus aureusPreprint
Wongdontree, P., Palmier, M., Louche, C., Léguillier, V., Rodrigues, C. M., Gloux, K., Halpern, D., Henry, C., Anba‐Mondoloni, J., & Gruss, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.18.629266
Cai, L., Wang, H., Xie, Y., Xu, X., & Zhou, G. (2025) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2025.105471
Contrôle de la résistance aux antibiotiques par des ARN régulateurs
Baussier, C. (2023) · theses.fr (ABES) · doi:10.70675/f49c0a6bz58a5z4e8fz8691z0e7220d5adab
Control of the iron-sparing response in Staphylococcus aureus by a regulatory RNA
Barrault, M. (2023) · theses.fr (ABES) · doi:10.70675/6d13b6e4zd6f9z42bdz8c5bz5262c5da4c10
Self-citationKumeko, E. K., Hatin, I., Chabelskaya, S., Corler, E., Namy, O., & Bouloc, P. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.22.726194
“Our Ribo-seq experiments validated previously characterized IsrR targets ( narG , fdhA , miaB , and citB mRNAs), confirming the robustness of our approach (Barrault et al., 2024a; Barrault et al., 2024b; Coronel-Tellez et al., 2022; Rios-Delgado et al., 2024).”
InfluentialSelf-citationFabF and FadM cooperate to recycle fatty acids and rescue ∆plsX lethality in Staphylococcus aureus
Wongdontree, P., Palmier, M., Louche, C., Léguillier, V., Rodrigues, C. M., Gloux, K., Halpern, D., Henry, C., Anba‐Mondoloni, J., & Gruss, A. (2026) · PLoS Genetics · doi:10.1371/journal.pgen.1012165
“Deletions were confirmed by PCR and whole genome sequencing (S1 Table) and by RN-R ∆ plsX growth complementation in the absence of FAs using a plasmid-carried copy of the intact plsX gene (S2 Fig).”
Discovery of Staphylococcus aureus small RNAs highly expressed during human chronic infection
Briaud, P., Schumacher, J., & Whiteley, M. (2026) · mBio · doi:10.1128/mbio.00637-26
Hardman, B. L., & Sharples, G. J. (2026) · mSphere · doi:10.1128/msphere.00619-26
- Authors
- Coronel-Tellez, R. H., Pospiech, M., Barrault, M., Liu, W., Bordeau, V., Vasnier, C., Felden, B., Sargueil, B., & Bouloc, P.
- Affiliations
- Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) 91198, Gif-sur-Yvette , France
- Centre National de la Recherche Scientifique (FR)
- Bacterial RNAs & Medicine (FR)
- Corresponding author
- Bouloc, Philippe
- ORCID
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-07-29
- Volume
- 50
- Issue
- 15
- Pages
- 8529-8546
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC9410917
- OpenAlex
- W4288692482
- Cited by
- 43
- References
- 96
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 11
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- CNRS
- Université Paris-Saclay
- Inserm
- Université de Rennes 1
- Agence Nationale de la Recherche (ANR-15-CE12-0003-01)
- Fondation pour la Recherche Médicale (DBF20160635724)
- ANR (ANR-19-CE12-0006-01, ANR-19-CE45-0023-02)
- Université de Paris
- Consejo Nacional de Ciencia y Tecnología
- Agence Nationale de la Recherche contre le SIDA fellowship (ANRS-A02019-2 ECTZ108689)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- small RNA, Staphylococcus aureus, iron starvation, anaerobic nitrate respiration, translation repression, iron-containing enzymes, Staphylococcus
- MeSH terms
- Animals, Bacteria, Humans, Iron, RNA, Bacterial, RNA, Messenger, Staphylococcus, Staphylococcus aureus, Gene Expression Regulation, Bacterial, Mice, RNA, Small Untranslated
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