sRNA-controlled iron sparing response in Staphylococci

Coronel-Tellez, Rodrigo H; Pospiech, Mateusz; Barrault, Maxime; Liu, Wenfeng; Bordeau, Valérie; Vasnier, Christelle; Felden, Brice; Sargueil, Bruno; Bouloc, Philippe

doi:10.1093/nar/gkac648

Cited by 26 publications

(68 citation statements)

References 96 publications

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“…This result is interpreted as iron depletion leading to apo-MiaB being unstable. To overcome this issue, a fur ::tet allele (20) was introduced by phage-mediated transduction in the miaB-flag and Δ isrR miaB-flag strains rendering isrR constitutively expressed (3). Expectedly, in this genetic background, MiaB-Flag was barely visible in the fur strain as opposed to its fur Δ isrR derivative (Figure 2C).…”

Section: Resultsmentioning

confidence: 99%

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StaphylococcalsRNA IsrR down-regulates methylthiotransferase MiaB under iron-deficient conditions

Barrault,

Leclair,

Kumeko

et al. 2023

Preprint

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Staphylococcus aureusis a major contributor to bacterial-associated mortality, owing to its exceptional adaptability across diverse environments. Iron, vital for most organisms, poses toxicity risks in excess. To manage iron,S. aureus, like many pathogens, employs intricate systems. We have recently identified IsrR as a key regulatory RNA induced during iron starvation. Its role is to curtail the synthesis of non-essential iron-containing proteins under iron-depleted conditions. In this study, we unveil IsrR’s regulatory action on MiaB, an enzyme responsible for methylthio group addition to specific sites on transfer RNAs (tRNAs). We use predictive tools and reporter fusion assays to demonstrate IsrR’s binding to the Shine-Dalgarno sequence ofmiaBRNA, thereby impeding its translation. The effectiveness of IsrR hinges on the integrity of a specific C-rich region. As MiaB is non-essential and contains two [4Fe-4S] clusters, IsrR induction spares iron by downregulatingmiaB. This likely enhancesS. aureusfitness and aids in navigating the host’s nutritional immune defenses.IMPORTANCEIn numerous biotopes, including those found within an infected host, bacteria confront the challenge of iron deficiency. They employ various strategies to adapt to this scarcity of nutrients, one of which involves the regulation of iron-containing proteins through the action of small regulatory RNAs. In our study, we demonstrate how IsrR, a small RNA fromS. aureus, inhibits the translation of MiaB, a tRNA-modifying enzyme containing [Fe-S] clusters. Through this illustration, we shed light on a novel substrate for a small RNA sparing iron, thereby unveiling a way by which bacteria conserve their iron resource.

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Section: Resultsmentioning

confidence: 99%

“…We recently identified and characterized IsrR, a regulatory RNA of S. aureus , contributing to an adaptive response to iron scarcity (3). By restricting non-essential iron-containing protein synthesis, IsrR spares iron for indispensable functions.…”

Section: Introductionmentioning

confidence: 99%

StaphylococcalsRNA IsrR down-regulates methylthiotransferase MiaB under iron-deficient conditions

Barrault,

Leclair,

Kumeko

et al. 2023

Preprint

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“…In addition to Fe acquisition, many bacteria respond to Fe limitation by repressing the synthesis of non-essential Fe-containing proteins and sparing intracellular Fe for essential cellular functions [ 11 ]. This strategy has been observed in B. subtilis , Caulobacter crescentus , Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus [ 12 , 13 , 14 , 15 , 16 ]. Notably, these alterant Fe-containing proteins in different bacteria are various under Fe deficiency.…”

Section: Introductionmentioning

confidence: 95%

Comprehensive Genomics and Proteomics Analysis Reveals the Multiple Response Strategies of Endophytic Bacillus sp. WR13 to Iron Limitation

et al. 2023

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Iron (Fe) is an important metal element for the growth of bacteria. Many bacteria respond to Fe limitation through a variety of strategies. We previously isolated an endophyte Bacillus sp. WR13 from wheat root. However, whether and how this strain can cope with Fe-deficient environments remains unclear. In this study, the growth of WR13 under Fe starvation was investigated, and the underlying mechanisms of WR13 in response to Fe starvation were elucidated via genomics and iTRAQ-based proteomics. Under Fe limitation, WR13 showed a growth pattern similar to that of Fe sufficiency. Genomics analysis demonstrated that WR13 had gene clusters related to siderophore synthesis (dhbACEBF), transportation (bcbE), uptake (feuABC-yusV) and hydrolysis (besA). These genes were significantly up-regulated in Fe-starved WR13, which resulted in more siderophore production. Proteomics data revealed that many Fe-containing proteins such as ACO, HemQ, ferredoxin, CNP, and SufD were significantly reduced under Fe limitation. Meanwhile, significant decreases in many proteins involved in glycolysis, TCA cycle, pentose phosphate pathway; asparagine, glutamine, methionine, and serine metabolism; and phospholipid hydrolysis were also observed. Overall, this study shows that Bacillus sp. WR13 was able to respond to Fe limitation via multiple strategies and provides a theoretical basis for the application of WR13 in Fe-deficient soil.

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“…When the bioavailable concentration of Fe is low, Fur is demetallated and repression is relieved. Fur often also controls the expression of a sRNA ( tsr25 in S. aureus ) that helps to optimize Fe usage (12).…”

Section: Introductionmentioning

confidence: 99%

YlaN is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression inStaphylococcus aureus

Boyd,

Esquilín-Lebrón,

Campbell

et al. 2023

Preprint

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Iron (Fe) is a trace nutrient required by nearly all organisms. As a result of the demand for Fe and the toxicity of non-chelated cytosolic ionic Fe, regulatory systems have evolved to tightly balance Fe acquisition and usage while limiting overload. In most bacteria, including the mammalian pathogenStaphylococcus aureus, the ferric uptake regulator (Fur) is the primary transcriptional regulator that controls the transcription of genes that code for Fe uptake and utilization proteins. YlaN was demonstrated to be essential inBacillus subtilisunless excess Fe is added to the growth medium, suggesting a role in Fe homeostasis. Here, we demonstrate that YlaN is expendable inS. aureus; however, YlaN became essential upon Fe deprivation. A nullfurallele bypassed the essentiality of YlaN. The transcriptional response of Fur derepression resulted in a reprogramming of metabolism to prioritize fermentative growth over respiratory growth. The absence of YlaN diminished the derepression of Fur-dependent transcription during Fe limitation. Bioinformatic analyses suggest thatylaNwas recruited to Gram positive bacteria and once acquired was maintained in the genome as it co-evolved with Fur. Consistent with a role for YlaN in influencing Fur-dependent regulation, YlaN and Fur interactedin vivo. YlaN bound Fe(II)in vitrousing oxygen or nitrogen ligands with an association constant that is consistent with a physiological role in Fe sensing and/or buffering. These findings have led to a model wherein YlaN is an Fe(II) binding protein that influences Fur-dependent regulation through direct interaction.ImportanceIron (Fe) is an essential nutrient for nearly all organisms. If Fe homeostasis is not maintained, Fe can accumulate in the cytosol where it is toxic. Questions remain about how cells efficiently balance Fe uptake and usage to prevent imbalance. Iron uptake and proper metalation of proteins are essential processes in the mammalian bacterial pathogenStaphylococcus aureus. Understanding the gene products involved in Fe ion regulation, uptake, and usage, as well as the physiological adaptations thatS. aureususes to survive in Fe-depleted conditions, will provide insight into the role that Fe has in pathogenesis. These data will also provide insight into the selective pressures imparted by the mammalian host.

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sRNA-controlled iron sparing response in Staphylococci

Cited by 26 publications

References 96 publications

StaphylococcalsRNA IsrR down-regulates methylthiotransferase MiaB under iron-deficient conditions

StaphylococcalsRNA IsrR down-regulates methylthiotransferase MiaB under iron-deficient conditions

Comprehensive Genomics and Proteomics Analysis Reveals the Multiple Response Strategies of Endophytic Bacillus sp. WR13 to Iron Limitation

YlaN is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression inStaphylococcus aureus

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