scholarly journals The Staphylococcus aureus GGDEF Domain-Containing Protein, GdpS, Influences Protein A Gene Expression in a Cyclic Diguanylic Acid-Independent Manner

2009 ◽  
Vol 77 (7) ◽  
pp. 2849-2856 ◽  
Author(s):  
Fei Shang ◽  
Ting Xue ◽  
Haipeng Sun ◽  
Lei Xing ◽  
Shuo Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Protein A ◽  
Surface Protein ◽  
Transcript Level ◽  
Cysteine Proteases ◽  
Independent Manner ◽  
Wide Range ◽  
Ggdef Domain ◽  
Major Surface

ABSTRACT Staphylococcus aureus is an important human pathogen that is the principal cause of a variety of diseases, ranging from localized skin infections to life-threatening systemic infections. The success of the organism as a pathogen and its ability to cause such a wide range of infections are due to its extensive virulence factors. In this study, we identified the role of the only GGDEF domain protein (GdpS [GGDEF domain protein from Staphylococcus]) in the virulence of S. aureus NCTC8325. Inactivation of gdpS results in an alteration in the production of a range of virulence factors, such as serine and cysteine proteases, fibrinogen-binding proteins, and, specifically, protein A (Spa), a major surface protein of S. aureus. The transcript level of spa decreases eightfold in the gdpS mutant compared with the parental NCTC8325 strain. Furthermore, the transcript level of sarS, which encodes a direct positive regulator of spa, also decreases in the gdpS mutant compared with the wild type, while the transcript levels of agr, sarA, sarT, and rot display no apparent changes in the gdpS mutant, suggesting that GdpS affects the expression of spa through interaction with SarS by unknown mechanisms. Furthermore, the complementation assays show that the influences of GdpS on spa and sarS depend on its N-terminal domain, which is predicted to be the sensor of a two-component system, rather than its C-terminal GGDEF domain with conserved GGDEF, suggesting that GdpS functions in S. aureus by an unknown mechanism independent of 3′,5′-cyclic diguanylic acid signaling.

scholarly journals Immunity induced by Staphylococcus aureus surface protein A was protective against lethal challenge of Staphylococcus aureus in BALB/c mice

2012 ◽  
Vol 56 (6) ◽  
pp. 406-410 ◽  
Author(s):  
Shao-Qiong Yi ◽  
Xiao-Yan Zhang ◽  
Yi-Long Yang ◽  
Yue Yang ◽  
Shu-Ling Liu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Surface Protein ◽  
Lethal Challenge

scholarly journals Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149460 ◽  
Author(s):  
Yilong Yang ◽  
Mengying Qian ◽  
Shaoqiong Yi ◽  
Shuling Liu ◽  
Bing Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibody ◽  
Protein A ◽  
Surface Protein ◽  
Antibody Targeting

scholarly journals The Staphylococcus aureus Protein-Coding GenegdpSModulatessarSExpression via mRNA-mRNA Interaction

2015 ◽  
Vol 83 (8) ◽  
pp. 3302-3310 ◽  
Author(s):  
Chuan Chen ◽  
Xu Zhang ◽  
Fei Shang ◽  
Haipeng Sun ◽  
Baolin Sun ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Environmental Changes ◽  
Wide Spectrum ◽  
Protein A ◽  
Mrna Levels ◽  
Site Mutation ◽  
Transcript Levels ◽  
Content Type ◽  
Ggdef Domain ◽  
Domain Protein

Staphylococcus aureusis an important Gram-positive pathogen responsible for numerous diseases ranging from localized skin infections to life-threatening systemic infections. The virulence ofS. aureusis essentially determined by a wide spectrum of factors, including cell wall-associated proteins and secreted toxins that are precisely controlled in response to environmental changes. GGDEF domain protein fromStaphylococcus(GdpS) is the only conserved staphylococcal GGDEF domain protein that is involved not in c-di-GMP synthesis but in the virulence regulation ofS. aureusNCTC8325. Our previous study showed that the inactivation ofgdpSgenerates an extensive change of virulence factors together with, in particular, a major Spa (protein A) surface protein. As reported,sarSis a direct positive regulator ofspa. The decreased transcript levels ofsarSin thegdpSmutant compared with the parental NCTC8325 strain suggest thatgdpSaffectsspathrough interaction withsarS. In this study, site mutation and complementary experiments showed that the translation product ofgdpSwas not involved in the regulation of transcript levels ofsarS. We found thatgdpSfunctioned through direct RNA-RNA base pairing with the 5′ untranslated region (5′UTR) ofsarSmRNA and that a putative 18-nucleotide region played a significant role in the regulatory process. Furthermore, the mRNA half-life analysis ofsarSin thegdpSmutant showed thatgdpSpositively regulates the mRNA levels ofsarSby contributing to the stabilization ofsarSmRNA, suggesting thatgdpSmRNA may regulatespaexpression in an RNA-dependent pathway.

scholarly journals Transcriptional Profiling of Target of RNAIII-Activating Protein, a Master Regulator of Staphylococcal Virulence

2005 ◽  
Vol 73 (10) ◽  
pp. 6220-6228 ◽  
Author(s):  
Moshe Korem ◽  
Yael Gov ◽  
Madanahally D. Kiran ◽  
Naomi Balaban
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Transcriptional Profiling ◽  
Protein A ◽  
Cell Communication ◽  
Global Regulator ◽  
Positive Bacterium ◽  
Master Regulator ◽  
Expression Of Genes ◽  
Histidine Phosphorylation

ABSTRACT Staphylococcus aureus is a gram-positive bacterium that is part of the normal healthy flora but that can become virulent and cause infections by producing biofilms and toxins. The production of virulence factors is regulated by cell-cell communication (quorum sensing) through the histidine phosphorylation of target of RNAIII-activating protein (TRAP), which is a 21-kDa protein that is highly conserved among staphylococci. Using microarray analysis, we show here that the expression and phosphorylation of TRAP upregulate the expression of most, if not all, toxins known to date, as well as their global regulator agr. In addition, we show here that the expression and phosphorylation of TRAP are also necessary for the expression of genes known to be necessary for the survival of the bacteria in a biofilm, like arc, pyr, and ure. TRAP is thus demonstrated to be a master regulator of staphylococcal pathogenesis.

scholarly journals Simultaneous lack of catalase and beta-toxin in Staphylococcus aureus leads to increased intracellular survival in macrophages and epithelial cells and to attenuated virulence in murine and ovine models

Microbiology ◽  
2009 ◽  
Vol 155 (5) ◽  
pp. 1505-1515 ◽  
Author(s):  
Susana Martínez-Pulgarín ◽  
Gustavo Domínguez-Bernal ◽  
José A. Orden ◽  
Ricardo de la Fuente
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Epithelial Cells ◽  
Virulence Factors ◽  
Mammary Epithelial Cells ◽  
Intracellular Survival ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Wide Range ◽  
Beta Toxin

Staphylococcus aureus produces a variety of virulence factors that allow it to cause a wide range of infections in humans and animals. In the latter, S. aureus is a leading cause of intramammary infections. The contribution of catalase (KatA), an enzyme implicated in oxidative stress resistance, and beta-toxin (Hlb), a haemolysin, to the pathogenesis of S. aureus is poorly characterized. To investigate the role of these enzymes as potential virulence factors in S. aureus, we examined the intracellular survival of ΔkatA, Δhlb and ΔkatA Δhlb mutants in murine macrophages (J774A.1) and bovine mammary epithelial cells (MAC-T), and their virulence in different murine and ovine models. Catalase was not required for the survival of S. aureus within either J774A.1 or MAC-T cells. However, it was necessary for the intracellular proliferation of the bacterium after invasion of MAC-T cells. In addition, catalase was not needed for the full virulence of S. aureus in mice. Deletion of the hlb gene had no effect on the intracellular survival of S. aureus in J774A.1 cells but did cause a slight increase in survival in MAC-T cells. Furthermore, like catalase, beta-toxin was not required for complete virulence of S. aureus in murine models. Unexpectedly, the ΔkatA Δhlb mutant showed a notably increased persistence in both cell lines, and was significantly less virulent for mice than were the wild-type strain and single mutants. Most interestingly, it was also markedly attenuated in intramammary and subcutaneous infections in ewes and lambs.

scholarly journals Subinhibitory Concentrations of Linezolid Reduce Staphylococcus aureus Virulence Factor Expression

2004 ◽  
Vol 48 (2) ◽  
pp. 546-555 ◽  
Author(s):  
Katussevani Bernardo ◽  
Norbert Pakulat ◽  
Silke Fleer ◽  
Annabelle Schnaith ◽  
Olaf Utermöhlen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Polyacrylamide Gel Electrophoresis ◽  
Protein A ◽  
Sodium Dodecyl ◽  
Elongation Factor ◽  
Dependent Manner ◽  
Triacylglycerol Lipase ◽  
Subinhibitory Concentrations ◽  
Dose Dependent

ABSTRACT The influence of the antibiotic linezolid on the secretion of exotoxins by Staphylococcus aureus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot analysis. S. aureus suspensions were treated with grading subinhibitory concentrations of linezolid (12.5, 25, 50, and 90% of MIC) at different stages of bacterial growth (i.e., an optical density at 540 nm [OD540] of 0.05 or 0.8). When added to S. aureus cultures at an OD540 of 0.05, linezolid reduced in a dose-dependent manner the secretion of specific virulence factors, including staphylococcal enterotoxin A (SEA) and SEB, bifunctional autolysin, autolysin, protein A, and alpha- and beta-hemolysins. In contrast, other presumably nontoxic exoproteins remained unchanged or even accumulated in supernatants in the presence of linezolid at a 90% MIC. Similarily, when added at OD540 of 0.8, that is, after quorum sensing, linezolid reduced the release of virulence factors, whereas the relative abundance of nontoxic exoproteins such as triacylglycerol lipase, glycerol ester hydrolase, DnaK, or translation elongation factor EF-Tu was found to be increased. Consistently, linezolid reduced in a dose-dependent manner the tumor necrosis factor-inducing activity secreted by S. aureus into the culture supernatants. The results of our study suggest that the expression of virulence factors in S. aureus is especially sensitive to the inhibition of protein synthesis by linezolid, which should be an advantage in the treatment of infections with toxin-producing S. aureus.

scholarly journals Staphylococcus aureus Arsenal To Conquer the Lower Respiratory Tract

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Mariane Pivard ◽  
Karen Moreau ◽  
François Vandenesch
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Tract ◽  
Virulence Factors ◽  
Lower Respiratory Tract ◽  
Defense Mechanisms ◽  
Future Research ◽  
Epithelial Barrier ◽  
Content Type ◽  
Wide Range ◽  
The Impact

ABSTRACT Staphylococcus aureus is both a commensal and a pathogenic bacterium for humans. Its ability to induce severe infections is based on a wide range of virulence factors. S. aureus community-acquired pneumonia (SA-CAP) is rare and severe, and the contribution of certain virulence factors in this disease has been recognized over the past 2 decades. First, the factors involved in metabolism adaptation are crucial for S. aureus survival in the lower respiratory tract, and toxins and enzymes are required for it to cross the pulmonary epithelial barrier. S. aureus subsequently faces host defense mechanisms, including the epithelial barrier, but most importantly the immune system. Here, again, S. aureus uses myriad virulence factors to successfully escape from the host’s defenses and takes advantage of them. The impact of S. aureus virulence, combined with the collateral damage caused by an overwhelming immune response, leads to severe tissue damage and adverse clinical outcomes. In this review, we summarize step by step all of the S. aureus factors implicated in CAP and described to date, and we provide an outlook for future research.

scholarly journals Rat/MgrA, a Regulator of Autolysis, Is a Regulator of Virulence Genes in Staphylococcus aureus

2005 ◽  
Vol 73 (3) ◽  
pp. 1423-1431 ◽  
Author(s):  
Susham Ingavale ◽  
Willem van Wamel ◽  
Thanh T. Luong ◽  
Chia Y. Lee ◽  
Ambrose L. Cheung
Keyword(s):  
Staphylococcus Aureus ◽  
Gene Product ◽  
Regulatory Network ◽  
Virulence Genes ◽  
Protein A ◽  
Northern Analysis ◽  
Independent Manner ◽  
Autolytic Activity

ABSTRACT We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of α-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and vice versa, indicating that MgrA likely regulates hla and spa in a SarA-independent manner. Previously we have shown that SarT, a SarA homolog, is a repressor of hla and an activator of spa, presumably by activating SarS, however, analysis of the double sarT mgrA mutant for hla and spa transcription indicated that the mgrA-mediated effect is not mediated via sarT. Our results further demonstrated that the mgrA gene product regulates hla and spa expression in a dual fashion, with the first being agr dependent and the second agr independent. In the agr-independent pathway, MgrA binds directly to hla and the sarS promoter to modulate α-hemolysin and protein A expression. Thus, our studies here have defined the nature of interaction of mgrA with other regulators such as agr, sarS, and sarT and its role in regulating hla and spa transcription within the virulence regulatory network of S. aureus.

scholarly journals Defense against own arms: staphylococcal cysteine proteases and their inhibitors.

2003 ◽  
Vol 50 (3) ◽  
pp. 715-724 ◽  
Author(s):  
Grzegorz Dubin
Keyword(s):  
Staphylococcus Aureus ◽  
Protease Inhibitors ◽  
Current Knowledge ◽  
Cysteine Proteases ◽  
Infection Process ◽  
Secreted Proteins ◽  
Human Pathogen ◽  
Cysteine Protease Inhibitors ◽  
Wide Range

Staphylococcus aureus is a human pathogen causing a wide range of diseases. Most staphylococcal infections, unlike those caused by other bacteria are not toxigenic and very little is known about their pathogenesis. It has been proposed that a core of secreted proteins common to many infectious strains is responsible for colonization and infection. Among those proteins several proteases are present and over the years many different functions in the infection process have been attributed to them. However, little direct, in vivo data has been presented. Two cysteine proteases, staphopain A (ScpA) and staphopain B (SspB) are important members of this group of enzymes. Recently, two cysteine protease inhibitors, staphostatin A and staphostatin B (ScpB and SspC, respectively) were described in S. aureus shedding new light on the complexity of the processes involving the two proteases. The scope of this review is to summarize current knowledge on the network of staphylococcal cysteine proteases and their inhibitors in view of their possible role as virulence factors.

scholarly journals Virulence factors and antimicrobial resistance of Staphylococcus aureus isolated from bovine mastitis in Rio de Janeiro

2009 ◽  
Vol 29 (5) ◽  
pp. 369-374 ◽  
Author(s):  
Shana M.O. Coelho ◽  
Elina Reinoso ◽  
Ingrid A. Pereira ◽  
Lidiane C. Soares ◽  
Mirta Demo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Protein A ◽  
Bovine Mastitis ◽  
Subclinical Mastitis ◽  
Resistance Pattern ◽  
Igg Binding ◽  
Amplicon Size ◽  
Resistance To Penicillin ◽  
Single Amplicon

The study was conducted to characterize pheno-genotypically the virulence factors and resistance pattern of Staphylococcus aureus isolates from milk samples of cows with subclinical mastitis. All hemolytic isolates presented beta-hemolysin, and 38% of the non-hemolytic isolates were able to express hemolysins in the presence of a beta-hemolytic strain. The amplification of the coa-gene displayed four different size polymorphisms with about 400 bp, 600 bp, 700 bp and 900 bp. The spaA gene that encodes the IgG-binding region of protein A revealed sizes of 700 bp and 900 bp. The amplification of region X from spaA yielded a single amplicon for each isolate with the prevalent amplicon size being of 180 bp. Amplification of sae gene yielded an amplicon size of 920 bp in 71% of the isolates. Antibiotic resistance pattern revealed that 42% S. aureus were susceptible to all antimicrobials tested. Seven different antibiotic patterns were observed. Our results indicated that 47% and 25% of S. aureus strains exhibited resistance to penicillin and oxacillin respectively. All oxacillin-resistant isolates were mecA-positive.

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