Global repression of exotoxin synthesis by staphylococcal superantigens

Vojtov, Nikola; Ross, Hope F.; Novick, Richard P.

doi:10.1073/pnas.152152499

Cited by 96 publications

(71 citation statements)

References 33 publications

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“…Plasmid-carried ␤-lactamase fusions involving P hla , P tst , and P sspA were introduced into various strains and tested for ␤-lactamase activity during growth at pH 5.5 versus 7.5. The promoters for these three exoprotein genes were selected because, although postexponentially up-regulated by agr, they are regulated differentially by sar and sae (8,36,52; for a review, see the report of Novick 34). Results for the ␤-lactamase fusions are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Effect of Mild Acid on Gene Expression in Staphylococcus aureus

et al. 2004

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During staphylococcal growth in glucose-supplemented medium, the pH of a culture starting near neutrality typically decreases by about 2 units due to the fermentation of glucose. Many species can comfortably tolerate the resulting mildly acidic conditions (pH, ϳ5.5) by mounting a cellular response, which serves to defend the intracellular pH and, in principle, to modify gene expression for optimal performance in a mildly acidic infection site. In this report, we show that changes in staphylococcal gene expression formerly thought to represent a glucose effect are largely the result of declining pH. We examine the cellular response to mild acid by microarray analysis and define the affected gene set as the mild acid stimulon. Many of the genes encoding extracellular virulence factors are affected, as are genes involved in regulation of virulence factor gene expression, transport of sugars and peptides, intermediary metabolism, and pH homeostasis. Key results are verified by gene fusion and Northern blot hybridization analyses. The results point to, but do not define, possible regulatory pathways by which the organism senses and responds to a pH stimulus.Facultative pathogens such as staphylococci produce a wide variety of accessory proteins. Many of these are involved in, or required for, infectivity and are collectively referred to as the virulon. It is widely believed that the genes encoding these proteins are regulated according to the exigencies of the local sites in which the organism is able to establish an infection. The evidence in support of this very logical view is, at best, rather sketchy, largely for two reasons. Firstly, it has, until very recently, been unapproachably difficult to determine the putative locale-specific gene expression patterns. Secondly, it has been no easy matter to identify the specific environmental factors that would determine these patterns. As a preamble to the ultimate objective of defining in vivo environmental factors that influence the expression of accessory genes involved in local pathogenesis, we have begun to reexamine the effect of certain nutrients and other chemicals, including glucose, acidic pH, salt, salicylic acid, and subinhibitory concentrations of antibiotics, on the expression of virulence genes during growth in vitro. These substances have widespread effects on the transcription of virulence genes and other accessory genes, which are presumably initiated through signaling elements and mediated through the complex regulatory network that governs the expression of all accessory genes (34). Our entrée into the transduction of environmental signals was provided by the observation that all of these substances affected transcription of a key signaling locus, sae, which is involved in the regulation of the expression of many exoproteins (36). In that study, which was initiated by a determination of the effect of glucose, it was shown that sae has a complex transcriptional pattern that undergoes a very striking switch during in vitro growth at neutral pH, in which...

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Section: Resultsmentioning

confidence: 99%

Effect of Mild Acid on Gene Expression in Staphylococcus aureus

et al. 2004

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“…Prophage incorporation into the S. aureus results in increased ability of the bacteria to colonize the host tissue by ecological adaptation to human host, evasion from the immune system and production of virulence factors (5,7). A posasible contributor to this increased virulence is PantonValentine leukocidin (PVL), the prophage-encoded toxin responsible for necrotizing pneumonitis, which can be fatal within 24-48 hours, as recently described.…”

Section: Introductionmentioning

confidence: 92%

“…A posasible contributor to this increased virulence is PantonValentine leukocidin (PVL), the prophage-encoded toxin responsible for necrotizing pneumonitis, which can be fatal within 24-48 hours, as recently described. Superantigens are among the other important staphylococcal virulence factors; they are responsible for food poisoning, toxic shock syndrome (TSS) and necrotizing fasciitis (7).…”

Section: Introductionmentioning

confidence: 99%

Prophage Typing of Methicillin Resistant Staphylococcus aureus Isolated from a Tertiary Care Hospital in Tehran, Iran

Rahimi

Bouzari

Katouli

et al. 2012

Jundishapur J Microbiol

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This study has highlighted the presence of bacteriophage types among MRSA isolates to show the high potential of these isolates to produce broad spectrum of virulence factors. Background:Staphylococcus aureus is a common cause of infections among humans and animals and it is known as a community-acquired and nosocomial pathogen. Most of the isolates contain lysogenic phages which are responsible for production of various virulence factors such as enterotoxins, staphylokinase, β-lysin, lipase, exfoliative toxin A and Pantone-vlaentine leukociden (PVL). All staphylococcus isolates are classified in 6 groups according to their sensitivity to 27 known lysogenic phages. Objectives: This study was performed to detect the presence of bacteriophage types and determine antibiotic resistance pattern of methicillin resistant S. aureus (MRSA) isolates obtained from a tertiary care hospital in Tehran, Iran from 2008 to 2010. Materials and Methods: A total of 968 S. aureus isolates were collected from a tertiary care hospital in Tehran, Iran and identified at the species level by PCR and biochemical tests. Susceptibility to 17 antibiotics was determined. Then oxacillin and vancomycin minimum inhibitory concentration (MIC) of the resistant isolates were determined. Multiplex-PCR was used to detect 6 classes of prophages. Results: Out of the 968 isolates 247 isolates were resistant to methicillin. Highest antibiotic resistance was seen to penicillin (100%), erythromycin (89.8%), kanamycin (89.4%), ciprofloxacin (88.6%) and tobramycin (87.4) respectively. None of the MRSA isolates showed resistance to vancomycin, synercid and linezolid. MIC results indicated that 46.1 and 4.4% of isolates with high (MIC ≥ 128 µg/ml) and low level (MIC ≥ 4 µg/ml) showed resistance to oxacillin, respectively. Four different phage types and eight patterns of prophages were detected. All MRSA isolates contained at least one prophage. Totally, 2.8, 69.2 and 27.9% contained 5, 4 and 3 different prophage types, respectively. Conclusions: High prevalence of different classes of prophages indicating the potential to carry a broad spectrum of virulence factors and high oxacillin resistance were found in the MRSA isolates. Detection of SGF phage in 100% of the isolates indicates the ability of these isolates to produce virulence factors.

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“…Rather than contributing positively to T-cell toxicity, we found that the presence of the tst gene resulted in a decrease in the ability of a strain to lyse T cells. This could be explained by the findings of another study showing that TSST-1 has a global regulatory effect on exoprotein expression (17). To verify that TSST-1 and not some other factor in association with the gene for this protein was responsible for this, we compared the activity of a TSST-1-producing strain (strain RN4282 [7]) and an isogenic TSST-1 mutant (strain RN6938 [16]) (Fig.…”

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confidence: 98%

Identification of Factors Contributing to T-Cell Toxicity of Staphylococcus aureus Clinical Isolates

2008

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We examined the ability of 206 clinical isolates of Staphylococcus aureus to lyse T cells and found differences between Agr groups. We found that the beta and delta hemolysins are involved and that methicillin-resistant S. aureus strains are less toxic than methicillin-susceptible S. aureus strains.Staphylococcus aureus is a major human pathogen, and its ability to secrete toxins significantly contributes to host damage (3). Studies linking disease characteristics with specific genes in S. aureus are often hampered by the difficulty with the genetic manipulation of clinical isolates (18), the fact that laboratory strains are no longer a faithful representation of those causing disease today (5), and the fact that S. aureus often has multiple genes whose activities can be substituted for by other genes (4). In this study, we adopted an alternative approach, in that we took a large S. aureus strain collection and assayed a specific characteristic of each isolate. Because we had a large amount of genetic information (e.g., clonality by multilocus sequence type [MLST] [2] and the presence of 33 adhesins and toxins [11,13]) relating to this strain collection, we sought to make associations between these factors and toxicity.T cells are an important component of vertebrate immunity, although their role in protection against S. aureus infections is unclear. Using an immortalized T-cell line (T2 cells [15]), we developed an assay in which washed bacterial cells (grown in brain heart infusion medium overnight at 37°C shaking) were incubated with T cells (grown in RPMI [Gibco] supplemented with 10% fetal bovine serum [Gibco], 1 mM L-glutamine, 200 units/ml penicillin, and 0.1 mg/ml streptomycin [Sigma] at 37°C with 10% CO 2 ) for 30 min. The number of T cells lysed by the de novo production of proteins by S. aureus was measured by using trypan blue (Sigma) in a Fast-Read counting chamber (Immune Systems, United Kingdom). Table 1 shows the factors found to be associated with T-cell toxicity. The data could not be normalized, and so nonparametric tests were performed to identify associations between T-cell toxicity and a specific genetic factor(s). The first factor that was found to be associated with T-cell toxicity was Agr (accessory gene regulator) function. The Agr proteins are responsible for the down-regulation of surface proteins and the up-regulation of exoproteins when they reach a quorum (1) and are measured by determination of the level of expression of the delta toxin (11). The mean T-cell survival achieved when the T cells were incubated with strains expressing delta toxin was 59.2%, whereas 72.4% survival was achieved when the T cells were incubated with strains not expressing the delta toxin (P Ͻ 0.001, Mann-Whitney U test). As the delta toxin is itself a pore-forming protein, it is possible that our observation could be explained, at least in part, by the loss of this protein's expression alone and not as a result of the loss of other Agrregulated proteins.We next examined whether the presence of 16 other ...

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Global repression of exotoxin synthesis by staphylococcal superantigens

Cited by 96 publications

References 33 publications

Effect of Mild Acid on Gene Expression in Staphylococcus aureus

Effect of Mild Acid on Gene Expression in Staphylococcus aureus

Prophage Typing of Methicillin Resistant Staphylococcus aureus Isolated from a Tertiary Care Hospital in Tehran, Iran

Identification of Factors Contributing to T-Cell Toxicity of Staphylococcus aureus Clinical Isolates

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