Regulation of toxic shock syndrome toxin‐1 by the accessory gene regulator in <i>Staphylococcus aureus</i> is mediated by the repressor of toxins

Tuffs, Stephen W.; Herfst, Christine A.; Baroja, Miren L.; Podskalniy, Vladyslav A.; DeJong, Erica N.; Coleman, Charlotte E.; McCormick, John K.

doi:10.1111/mmi.14353

Cited by 19 publications

(18 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, SprY stimulates expression of the staphylococcal extracellular complement binding protein, Ecb ( 50 ) in an RNAIII-dependent manner. In accordance with positive regulation of rot , whose regulon includes genes encoding proteins with hemolytic activity such as hla , psmα and hlgACB ( 22 , 51 ), SprY reduces the hemolytic activity of S. aureus on human and mouse blood dependently from RNAIII presence.…”

Section: Discussionmentioning

confidence: 99%

A small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity

Huyen

González

Pascreau

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

Staphylococcus aureus is an opportunistic human and animal pathogen with an arsenal of virulence factors that are tightly regulated during bacterial infection. The latter is achieved through a sophisticated network of regulatory proteins and regulatory RNAs. Here, we describe the involvement of a novel prophage-carried small regulatory S. aureus RNA, SprY, in the control of virulence genes. An MS2-affinity purification assay reveals that SprY forms a complex in vivo with RNAIII, a major regulator of S. aureus virulence genes. SprY binds to the 13th stem-loop of RNAIII, a key functional region involved in the repression of multiple mRNA targets. mRNAs encoding the repressor of toxins Rot and the extracellular complement binding protein Ecb are among the targets whose expression is increased by SprY binding to RNAIII. Moreover, SprY decreases S. aureus hemolytic activity and virulence. Our results indicate that SprY titrates RNAIII activity by targeting a specific stem loop. Thus, we demonstrate that a prophage-encoded sRNA reduces the pathogenicity of S. aureus through RNA sponge activity.

show abstract

Section: Discussionmentioning

confidence: 99%

A small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity

Huyen

González

Pascreau

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…According to one current model, RNAIII upregulates tst transcription by blocking translation of r ot mRNA, thereby, relieving Rot repression of the tst promoter [ 14 , 15 , 23 , 36 ]. To investigate if ClpXP controls transcription of toxin genes via the RNAIII/Rot pathway, we determined the levels of RNAIII transcript and Rot protein in SA564Δ clpX and SA564Δ clpP cells in different growth phases.…”

Section: Resultsmentioning

confidence: 99%

“…The RNA-seq analysis, however, revealed a significant change in transcription of a number of genes encoding global virulence regulators, such as the SrrAB and AgrACBD, two component systems, and the SarA-like transcriptional regulators SarU, SarX, SarS, MgrA, and SarT (Table 1 and Table S1). Of these regulators, only Agr and SrrAB were previously confirmed to control the transcription of the tst gene [22,23,44,45]. In RN4282clpX I265E cells, transcription of RNAIII and the agrACBC operon was reduced 2-2.3-fold, a minor reduction that did not result in a diminished transcription of known RNAIII-controlled genes, such as hla (α-hemolysin), or the AgrA-controlled psmβ1 and psmβ2 (PSMs) genes- Table 1 and Table S1 [14,46].…”

Section: Rna-seq To Establish Transcriptional Regulators Involved In mentioning

confidence: 99%

“…The Agr system positively controls transcription of tst and select enterotoxin genes, like sed [ 12 , 17 , 18 , 19 , 20 , 21 ]. This agr- dependent upregulation of tst and sed transcription was proposed to be achieved via RNAIII-mediated downregulation of Rot (Repressor of toxin), thereby relieving Rot repression of the sed and tst genes [ 22 , 23 ]. Additionally, a large number of two-component systems, the alternative sigma factor, SigB, the ClpXP protease, and a number of transcriptional regulators, belonging to the family of SarA homologs, contribute to control S. aureus virulence genes expression [ 13 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Functional ClpXP Protease is Required for Induction of the Accessory Toxin Genes, tst, sed, and sec

Schelin

Cohn

Frisk

et al. 2020

Toxins

View full text Add to dashboard Cite

Staphylococcal toxic shock syndrome is a potentially lethal illness attributed to superantigens produced by Staphylococcus aureus, in particular toxic shock syndrome toxin 1 (TSST-1), but staphylococcal enterotoxins (SEs) are also implicated. The genes encoding these important toxins are carried on mobile genetic elements, and the regulatory networks controlling expression of these toxins remain relatively unexplored. We show here that the highly conserved ClpXP protease stimulates transcription of tst (TSST-1), sec (SEC), and sed (SED) genes in the prototypical strains, SA564 and RN4282. In the wild-type cells, the post-exponential upregulation of toxin gene transcription was proposed to occur via RNAIII-mediated downregulation of the Rot repressor. Contradictive to this model, we showed that the post-exponential induction of tst, sed, and sec transcription did not occur in cells devoid of ClpXP activity, despite the Rot level being diminished. To identify transcriptional regulators with a changed expression in cells devoid of ClpXP activity, RNA sequencing was performed. The RNAseq analysis revealed a number of global virulence regulators that might act downstream of ClpXP, to control expression of tst and other virulence genes. Collectively, the results extend our understanding of the complex transcriptional regulation of the tst, sed, and sec genes.

show abstract

“…SarA, a general transcriptional factor, can directly upregulate the expression of exoproteins [87] and the agr system [88], whereas it can downregulate the extracellular proteases during the biofilm formation [89]. Rot can induce the expression of surface proteins and repress the production of extracellular enzymes [90][91][92], which is suppressed by the effector RNAIII of the agr system [93,94]. MgrA acts as a negative regulator of biofilm formation by repressing the production of adhesins [95].…”

Section: Sara Family Proteinsmentioning

confidence: 99%

Biofilm and Small Colony Variants—An Update on Staphylococcus aureus Strategies toward Drug Resistance

Guo

Tong

Cheng

et al. 2022

IJMS

View full text Add to dashboard Cite

Recently, the drawbacks arising from the overuse of antibiotics have drawn growing public attention. Among them, drug-resistance (DR) and even multidrug-resistance (MDR) pose significant challenges in clinical practice. As a representative of a DR or MDR pathogen, Staphylococcus aureus can cause diversity of infections related to different organs, and can survive or adapt to the diverse hostile environments by switching into other phenotypes, including biofilm and small colony variants (SCVs), with altered physiologic or metabolic characteristics. In this review, we briefly describe the development of the DR/MDR as well as the classical mechanisms (accumulation of the resistant genes). Moreover, we use multidimensional scaling analysis to evaluate the MDR relevant hotspots in the recent published reports. Furthermore, we mainly focus on the possible non-classical resistance mechanisms triggered by the two important alternative phenotypes of the S. aureus, biofilm and SCVs, which are fundamentally caused by the different global regulation of the S. aureus population, such as the main quorum-sensing (QS) and agr system and its coordinated regulated factors, such as the SarA family proteins and the alternative sigma factor σB (SigB). Both the biofilm and the SCVs are able to escape from the host immune response, and resist the therapeutic effects of antibiotics through the physical or the biological barriers, and become less sensitive to some antibiotics by the dormant state with the limited metabolisms.

show abstract

Regulation of toxic shock syndrome toxin‐1 by the accessory gene regulator in Staphylococcus aureus is mediated by the repressor of toxins

Cited by 19 publications

References 37 publications

A small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity

A small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity

A Functional ClpXP Protease is Required for Induction of the Accessory Toxin Genes, tst, sed, and sec

Biofilm and Small Colony Variants—An Update on Staphylococcus aureus Strategies toward Drug Resistance

Contact Info

Product

Resources

About