Genome-scale transcriptional profiling in<i>Staphylococcus aureus</i>â: bringing order out of chaos

Nagarajan, Vijayaraj; Smeltzer, Mark S.; Elasri, Mohamed O.

doi:10.1111/j.1574-6968.2009.01595.x

Cited by 16 publications

(10 citation statements)

References 38 publications

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“…This underlines the findings of other studies demonstrating the importance of a multiple strain 245 investigation approach when studying regulatory elements (24, 43,44). This is the first study 246 investigating the effect of regulatory mutations (∆agr, ∆sarA, ∆sigB) on SED mRNA and protein 247 levels in several S. aureus strains other than derivatives of strain NCTC8325.…”

supporting

confidence: 83%

Effect of sodium nitrite and regulatory mutations Δagr, ΔsarA, and ΔsigB on the mRNA and protein levels of staphylococcal enterotoxin D

et al. 2016

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Staphylococcal food poisoning results from ingestion of enterotoxins produced by Staphylococcus aureus. Staphylococcal enterotoxin D (SED) is one of the most common toxins detected in S. aureus strains associated with intoxications. The effect of sodium nitrite on enterotoxin production has been only partly investigated, despite its wide usage in meat products. In addition, the factors influencing SED regulation are unclear. The aim of this study was to determine the effect of sodium nitrite on sed transcription and SED production, as well as the effect of regulatory mutations on SED protein levels. Temporal sed mRNA and SED protein levels were compared in LB and LB supplemented with 150 mg/L nitrite, and SED protein levels between wild type (wt) and isogenic regulatory mutants (Δagr, ΔsarA, ΔsigB) under control and sodium nitrite conditions. Relative sed mRNA levels of wt strains were higher in late stationary phase in the presence of nitrite compared to control conditions. However, SED protein levels were decreased in the presence of nitrite. In LB, Δagr mutants showed SED levels similar to the wt, while ΔsarA mutants exhibited reduced and ΔsigB mutants increased SED levels compared to the wt. In LB with sodium nitrite, SED levels of mutant strains were reduced similar to the wt strains, except for two Δagr mutants, in which SED levels were increased in the presence of nitrite. Overall, strain-specific variation with regard to the effect of regulatory mutations was observed. In addition, the data suggests that SED regulation may not be as tightly dependent on Agr as previously described.

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confidence: 83%

Effect of sodium nitrite and regulatory mutations Δagr, ΔsarA, and ΔsigB on the mRNA and protein levels of staphylococcal enterotoxin D

et al. 2016

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“…The production of SarA was unaffected by the functional status of saeRS, while expression of saeRS was reduced in a sarA mutant. This was previously reported to be the case in a COL sarA mutant [23], although it was not found to be the case in the clinical isolate UAMS-1 [24]. This suggests that this effect is strain-dependent.…”

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confidence: 72%

saeRS and sarA Act Synergistically to Repress Protease Production and Promote Biofilm Formation in Staphylococcus aureus

et al. 2012

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Mutation of the staphylococcal accessory regulator (sarA) limits biofilm formation in diverse strains of Staphylococcus aureus, but there are exceptions. One of these is the commonly studied strain Newman. This strain has two defects of potential relevance, the first being mutations that preclude anchoring of the fibronectin-binding proteins FnbA and FnbB to the cell wall, and the second being a point mutation in saeS that results in constitutive activation of the saePQRS regulatory system. We repaired these defects to determine whether either plays a role in biofilm formation and, if so, whether this could account for the reduced impact of sarA in Newman. Restoration of surface-anchored FnbA enhanced biofilm formation, but mutation of sarA in this fnbA-positive strain increased rather than decreased biofilm formation. Mutation of sarA in an saeS-repaired derivative of Newman (P18L) or a Newman saeRS mutant (ΔsaeRS) resulted in a biofilm-deficient phenotype like that observed in clinical isolates, even in the absence of surface-anchored FnbA. These phenotypes were correlated with increased production of extracellular proteases and decreased accumulation of FnbA and/or Spa in the P18L and ΔsaeRS sarA mutants by comparison to the Newman sarA mutant. The reduced accumulation of Spa was reversed by mutation of the gene encoding aureolysin, while the reduced accumulation of FnbA was reversed by mutation of the sspABC operon. These results demonstrate that saeRS and sarA act synergistically to repress the production of extracellular proteases that would otherwise limit accumulation of critical proteins that contribute to biofilm formation, with constitutive activation of saeRS limiting protease production, even in a sarA mutant, to a degree that can be correlated with increased enhanced capacity to form a biofilm. Although it remains unclear whether these effects are mediated directly or indirectly, studies done with an sspA::lux reporter suggest they are mediated at a transcriptional level.

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“…To begin to address the specificity of OHM for agr inhibition, we used qPCR to evaluate the effects of OHM on transcription of a series of agr-and non-agr-regulated genes involved in virulence, the stress response, metabolism, and drug efflux and resistance (14,25,48,49) (Table 1; see also Fig. S4 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

Daly

Elmore

Kavanaugh

et al. 2015

Antimicrob Agents Chemother

116

147

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d Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibility to host killing. Staphylococcus aureus is a major cause of invasive skin and soft tissue infections (SSTIs) in both the hospital and community settings, and it is also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by the accessory gene regulator (agr) controls virulence factor production essential for causing SSTIs. We recently identified -hydroxyemodin (OHM), a polyhydroxyanthraquinone isolated from solid-phase cultures of Penicillium restrictum, as a suppressor of QS and a compound sought for the further characterization of the mechanism of action. At concentrations that are nontoxic to eukaryotic cells and subinhibitory to bacterial growth, OHM prevented agr signaling by all four S. aureus agr alleles. OHM inhibited QS by direct binding to AgrA, the response regulator encoded by the agr operon, preventing the interaction of AgrA with the agr P2 promoter. Importantly, OHM was efficacious in a mouse model of S. aureus SSTI. Decreased dermonecrosis with OHM treatment was associated with enhanced bacterial clearance and reductions in inflammatory cytokine transcription and expression at the site of infection. Furthermore, OHM treatment enhanced the immune cell killing of S. aureus in vitro in an agr-dependent manner. These data suggest that bacterial disarmament through the suppression of S. aureus QS may bolster the host innate immune response and limit inflammation.

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Genome-scale transcriptional profiling inStaphylococcus aureusâ: bringing order out of chaos

Cited by 16 publications

References 38 publications

Effect of sodium nitrite and regulatory mutations Δagr, ΔsarA, and ΔsigB on the mRNA and protein levels of staphylococcal enterotoxin D

Effect of sodium nitrite and regulatory mutations Δagr, ΔsarA, and ΔsigB on the mRNA and protein levels of staphylococcal enterotoxin D

saeRS and sarA Act Synergistically to Repress Protease Production and Promote Biofilm Formation in Staphylococcus aureus

ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

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Genome-scale transcriptional profiling inStaphylococcus aureusâ: bringing order out of chaos

Cited by 16 publications

References 38 publications

Effect of sodium nitrite and regulatory mutations Δagr, ΔsarA, and ΔsigB on the mRNA and protein levels of staphylococcal enterotoxin D

Effect of sodium nitrite and regulatory mutations Δagr, ΔsarA, and ΔsigB on the mRNA and protein levels of staphylococcal enterotoxin D

saeRS and sarA Act Synergistically to Repress Protease Production and Promote Biofilm Formation in Staphylococcus aureus

ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

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Genome-scale transcriptional profiling inStaphylococcus aureusâ: bringing order out of chaos