Expanding the Staphylococcus aureus SarA Regulon to Small RNAs

Oriol, Charlotte; Cengher, Liviu; Manna, A. La; Mauro, Tony; Pinel-Marie, Marie-Laure; Felden, Brice; Cheung, Ambrose L.; Rouillon, Astrid

doi:10.1128/msystems.00713-21

Cited by 13 publications

(7 citation statements)

References 104 publications

(200 reference statements)

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“…After excluding ribosomal and phage genes, we focused on genes expressed at twofold higher and or lower (Table 2). Genes regulated by SarA, ribosomal genes, phage, and transposon genes were excluded from the analysis (Manna et al, 2018; Oriol et al, 2021). In the Teg49 mutant, there were 22 genes that had notable transcriptional changes due to Teg49 independent of SarA when compared to the parental strain.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus

Cengher

Manna

Cho

et al. 2022

Molecular Microbiology

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Teg49 is a Staphylococcus aureus trans‐acting regulatory sRNA derived from cleavage of the sarA P3 transcript. We showed by RNA‐Seq here that the 5′ trident‐like structure in Teg49 regulates transcriptionally (direct and indirect) 22 genes distinct from sarA. Among these, Teg49 was noted to repress spn, encoding a 102 residue preprotein which yields the mature 73 residue peptide which inhibits the catalytic activity of myeloperoxidase in human neutrophils. Teg49 was found to regulate spn mRNA post‐transcriptionally in strain SH1000 through 9‐nt base‐pairing between hairpin loop 2 of Teg49 and an exposed bulge of the spn mRNA. Mutations of the Teg49 binding site disrupted the repression of spn, leading to reduced degradation, and increased half‐life of spn mRNA in the Teg49 mutant. The spn‐Teg49 interaction was also confirmed with a synonymous spn mutation to yield enhanced spn expression in the mutant vs. the parent. The Teg49 mutant with increased spn expression exhibited enhanced resistance to MPO activity in vitro. Killing assays with human neutrophils showed that the Teg49 mutant was more resistant to killing after phagocytosis. Altogether, this study shows that Teg49 in S. aureus has a distinct and important regulatory profile whereby this sRNA modulates resistance to myeloperoxidase‐mediated killing by human neutrophils.

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Section: Resultsmentioning

confidence: 99%

“…RNA isolation and purification and subsequent Northern blot analysis were performed as described previously (Cheung et al, 1994; Manna et al, 2018; Oriol et al, 2021). Briefly, 15 μg of total RNAs were run on 8% polyacrylamide‐7 M urea gels and transferred onto Hybond‐N+ membranes (Amersham, USA) to detect sRNA.…”

Section: Methodsmentioning

confidence: 99%

Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus

Cengher

Manna

Cho

et al. 2022

Molecular Microbiology

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“…Those that regulate sRNA expression represent less than 10% of the TFs predicted (Table 4). Among them, the staphylococcal accessory regulator SarA is well studied and was shown to directly regulate 11 sRNAs, including RNAIII, Srn_3610_SprC, RsaD, and some sRNAs that are part of the toxin-antitoxin system, such as SprG2 or SprA2 AS [86,[186][187][188]. In their recent study, Oriol and colleagues combined the use of ChIPseq and RNA-Seq to conclude that the SarA sRNA regulon may encompass 51 sRNAs [188].…”

Section: Transcription Factors and Their Srna Regulonsmentioning

confidence: 99%

“…Among them, the staphylococcal accessory regulator SarA is well studied and was shown to directly regulate 11 sRNAs, including RNAIII, Srn_3610_SprC, RsaD, and some sRNAs that are part of the toxin-antitoxin system, such as SprG2 or SprA2 AS [86,[186][187][188]. In their recent study, Oriol and colleagues combined the use of ChIPseq and RNA-Seq to conclude that the SarA sRNA regulon may encompass 51 sRNAs [188]. Although some of them may not be direct targets, it is possible that the number of direct sRNA targets is underestimated.…”

Section: Transcription Factors and Their Srna Regulonsmentioning

confidence: 99%

Thirty Years of sRNA-Mediated Regulation in Staphylococcus aureus: From Initial Discoveries to In Vivo Biological Implications

Ménard

Silard

Suriray

et al. 2022

IJMS

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Staphylococcus aureus is a widespread livestock and human pathogen that colonizes diverse microenvironments within its host. Its adaptation to the environmental conditions encountered within humans relies on coordinated gene expression. This requires a sophisticated regulatory network, among which regulatory RNAs (usually called sRNAs) have emerged as key players over the last 30 years. In S. aureus, sRNAs regulate target genes at the post-transcriptional level through base–pair interactions. The functional characterization of a subset revealed that they participate in all biological processes, including virulence, metabolic adaptation, and antibiotic resistance. In this review, we report 30 years of S. aureus sRNA studies, from their discovery to the in-depth characterizations of some of them. We also discuss their actual in vivo contribution, which is still lagging behind, and their place within the complex regulatory network. These shall be key aspects to consider in order to clearly uncover their in vivo biological functions.

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“…SarA, a well-known S. aureus regulatory system, regulates the expression of many important virulence factors and induces S. aureus to produce biofilms, mainly by inhibiting the secretion of proteases ( Trotonda et al, 2005 ; Abdelhady et al, 2014 ). It has been reported that not only is the biofilm-forming ability of sarA mutants seriously damaged but it also leads to changes in the expression levels of at least 120 genes ( Mauro et al, 2016 ; Oriol et al, 2021 ). Numerous natural compounds, including thymol, carvacrol, and hesperidin, have been found to combat MRSA biofilms by targeting SarA ( Selvaraj et al, 2020 ; Yuan et al, 2020 ; Vijayakumar et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Geraniol inhibits biofilm formation of methicillin-resistant Staphylococcus aureus and increase the therapeutic effect of vancomycin in vivo

Ouyang

Hong

et al. 2022

Front. Microbiol.

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Methicillin-resistant Staphylococcus aureus (MRSA) is among the common drug resistant bacteria, which has gained worldwide attention due to its high drug resistance and infection rates. Biofilms produced by S. aureus are known to increase antibiotic resistance, making the treatment of S. aureus infections even more challenging. Hence, inhibition of biofilm formation has become an alternative strategy for controlling persistent infections. In this study, we evaluated the efficacy of geraniol as a treatment for MRSA biofilm infection. The results of crystal violet staining indicated that 256 μg/mL concentration of geraniol inhibited USA300 biofilm formation by 86.13% and removed mature biofilms by 49.87%. Geraniol exerted its anti-biofilm effect by influencing the major components of the MRSA biofilm structure. We found that geraniol inhibited the synthesis of major virulence factors, including staphyloxanthin and autolysins. The colony count revealed that geraniol inhibited staphyloxanthin and sensitized USA300 cells to hydrogen peroxide. Interestingly, geraniol not only reduced the release of extracellular nucleic acids (eDNA) but also inhibited cell autolysis. Real-time polymerase chain reaction data revealed the downregulation of genes involved in biofilm formation, which verified the results of the phenotypic analysis. Geraniol increased the effect of vancomycin in eliminating USA300 biofilms in a mouse infection model. Our findings revealed that geraniol effectively inhibits biofilm formation in vitro. Furthermore, in combination with vancomycin, geraniol can reduce the biofilm adhesion to the implant in mice. This suggests the potential of geraniol as an anti-MRSA biofilm drug and can provide a solution for the clinical treatment of biofilm infection.

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Expanding the Staphylococcus aureus SarA Regulon to Small RNAs

Abstract: Staphylococcus aureus , a commensal and opportunist pathogen, is responsible for a large number of human and animal infections, from benign to severe. Gene expression adaptation during infection requires a complex network of regulators, including transcriptional factors (TF) and sRNAs.

Cited by 13 publications

References 104 publications

Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus

Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus

Thirty Years of sRNA-Mediated Regulation in Staphylococcus aureus: From Initial Discoveries to In Vivo Biological Implications

Geraniol inhibits biofilm formation of methicillin-resistant Staphylococcus aureus and increase the therapeutic effect of vancomycin in vivo

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