Identification and characterization of msa (SA1233), a gene involved in expression of SarA and several virulence factors in Staphylococcus aureus

Sambanthamoorthy, Karthik; Smeltzer, Mark S.; Elasri, Mohamed O.

doi:10.1099/mic.0.29071-0

Cited by 38 publications

(50 citation statements)

References 57 publications

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“…This network consists of well-characterized loci, such as the agr two-component quorum sensor system (1,54); the various members of the SarA regulatory protein family, including SarS, SarT, SarU, SarV, SarX, SarZ, Rot, MgrA, and TcaR (17); the main stress response alternative sigma factor, SigB (7); and two-component sensortransducer systems saeRS (44), arlRS (42), and srrAB (61,76). Other loci with different attributed primary functions, or whose main functions are unknown, e.g., ccpA (70,71), spoVG (69), codY (60), msrR (33), and msa (65), have also been shown to contribute to virulence and/or to modulate virulence factor expression, creating links between virulence and other cellular traits such as metabolism and antibiotic resistance phenotypes.…”

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confidence: 99%

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

et al. 2010

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Transcription of spa, encoding the virulence factor protein A in Staphylococcus aureus, is tightly controlled by a complex regulatory network, ensuring its temporal expression over growth and at appropriate stages of the infection process. Transcriptomic profiling of XdrA, a DNA-binding protein that is conserved in all S. aureus genomes and shares similarity with the XRE family of helix-turn-helix, antitoxin-like proteins, revealed it to be a previously unidentified activator of spa transcription. To assess how XdrA fits into the complex web of spa regulation, a series of regulatory mutants were constructed; consisting of single, double, triple, and quadruple mutants lacking XdrA and/or the three key regulators previously shown to influence spa transcription directly (SarS, SarA, and RNAIII). A series of lacZ reporter gene fusions containing nested deletions of the spa promoter identified regions influenced by XdrA and the other three regulators. XdrA had almost as strong an activating effect on spa as SarS and acted on the same spa operator regions as SarS, or closely overlapping regions. All data from microarrays, Northern and Western blot analyses, and reporter gene fusion experiments indicated that XdrA is a major activator of spa expression that appears to act directly on the spa promoter and not through previously characterized regulators.

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Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

et al. 2010

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“…Previously, we identified and characterized the msaABCR operon and showed that it positively regulates expression of sarA, biofilm development, and virulence (33)(34)(35). Specifically, the msaABCR operon is a four-gene operon composed of msaA (SA1235), msaB (SA1234), msaC (SA1233), and newly discovered msaR antisense RNA (35).…”

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The msaABCR Operon Regulates Resistance in Vancomycin-Intermediate Staphylococcus aureus Strains

Samanta

Elasri

2014

Antimicrob Agents Chemother

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Vancomycin-intermediate Staphylococcus aureus (VISA) strains present an increasingly difficult problem in terms of public health. However, the molecular mechanism for this resistance is not yet understood. In this study, we define the role of the msaABCR operon in vancomycin resistance in three clinical VISA strains, i.e., Mu50, HIP6297, and LIM2. Deletion of the msaABCR operon resulted in significant decreases in the vancomycin MIC (from 6.25 to 1.56 g/ml) and significant reductions of cell wall thickness in strains Mu50 and HIP6297. Growth of the mutants in medium containing vancomycin at concentrations greater than 2 g/ml resulted in decreases in the growth rate, compared with the wild-type strains. Mutation of the msaABCR operon also reduced the binding capacity for vancomycin. We conclude that the msaABCR operon contributes to resistance to vancomycin and cell wall synthesis in S. aureus.

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“…The agr two-component system is one of the best-studied regulatory loci. Expression of agr is activated when bacterial cultures enter the postexponential growth phase in a cell densitydependent manner (34). Induction of agr expression results in RNAIII production, which leads to a reduced production of several surface proteins and facilitates the production of numerous extracellular proteins (29).…”

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Eugenol Reduces the Expression of Virulence-Related Exoproteins in Staphylococcus aureus

Qiu

Feng

Lü

et al. 2010

Appl Environ Microbiol

113

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Eugenol, an essential oil component in plants, has been demonstrated to possess activity against both Gram-positive and Gram-negative bacteria. This study examined the influence that subinhibitory concentrations of eugenol may have on the expression of the major exotoxins produced by Staphylococcus aureus. The results from a tumor necrosis factor (TNF) release assay and a hemolysin assay indicated that S. aureus cultured with graded subinhibitory concentrations of eugenol (16 to 128 g/ml) dose dependently decreased the TNF-inducing and hemolytic activities of culture supernatants. Western blot analysis showed that eugenol significantly reduced the production of staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1 (the key exotoxins to induce TNF release), as well as the expression of ␣-hemolysin (the major hemolysin to cause hemolysis). In addition, this suppression was also evaluated at the transcriptional level via real-time reverse transcription (RT)-PCR analysis. The transcriptional analysis indicated that 128 g/ml of eugenol remarkably repressed the transcription of the S. aureus sea, seb, tst, and hla genes. According to these results, eugenol has the potential to be rationally applied on food products as a novel food antimicrobial agent both to inhibit the growth of bacteria and to suppress the production of exotoxins by S. aureus.Staphylococcus aureus is a major nosocomial pathogen. This species is capable of causing a wide range of diseases and is often associated with high morbidity and mortality rates. The disease spectrum includes food-borne illness, cutaneous infections, endocarditis, pneumonia, septic arthritis, and osteomyelitis (24, 36). The diversity is, in part, dependent on the secretion of a broad spectrum of soluble extracellular proteins. These proteins include enterotoxins, hemolysins, toxic shock syndrome toxin 1 (TSST-1), and others (20). S. aureus infections are difficult to control due to a combination of toxinmediated virulence, invasiveness, and antibiotic resistance. Therefore, there is a continuing need to discover new and improved antimicrobial agents to treat S. aureus illnesses, with potential benefits for both the food and pharmaceutical industries (35).Enterotoxins, TSST-1, and ␣-hemolysin are among the major exotoxins secreted by S. aureus. Staphylococcal enterotoxins (SEs) are a group of major serological heat-stable enterotoxins (SEA to SEE and SEG to SEJ) (3). These toxins cause staphylococcal gastroenteritis, food poisoning, toxic shock-like syndromes, and several allergic and autoimmune diseases (3,22,35). TSST-1 is the key causative toxin of toxic shock syndrome (TSS), which is an acute-onset and potentially lifethreatening staphylococcal syndrome (23). Furthermore, SEs and TSST-1 are also known to be pyrogenic toxin superantigens (PTSAgs) that stimulate the proliferation of T lymphocytes and the release of T-cell-derived cytokines (12). ␣-Hemolysin is a 33-kDa pore-forming soluble protein that has hemolytic, cytolytic, and dermonecrotic activities....

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Identification and characterization of msa (SA1233), a gene involved in expression of SarA and several virulence factors in Staphylococcus aureus

Cited by 38 publications

References 57 publications

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

The msaABCR Operon Regulates Resistance in Vancomycin-Intermediate Staphylococcus aureus Strains

Eugenol Reduces the Expression of Virulence-Related Exoproteins in Staphylococcus aureus

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