Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.

ABSTRACT: Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus.

SUBMITTER: Tilahun AY

PROVIDER: S-EPMC4082930 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Chronic <i>Staphylococcus aureus</i> Superantigen Toxic Shock Syndrome Toxin-1 Exposure Accelerates the Progression of Atherosclerosis in Rabbits.

Project description:BackgroundIt has been reported that infectious agents contribute to the atherosclerotic process. However, it is unclear whether Staphylococcus aureus superantigen (SAg) toxic shock syndrome toxin-1 (TSST-1) has an effect on atherosclerosis progression. The present study was designed to investigate the pathogenic role of TSST-1 exposure in the atherosclerotic process in rabbits.MethodsNew Zealand White rabbits were exposed to TSST-1 through Alzet miniosmotic pumps with a constant pumping rate. Aortic atherosclerosis was evaluated by histological and morphometric methods. Using a biochemical analyzer/enzyme-linked immunosorbent assay/immunostaining, we further analyzed various atherosclerosis-related factors.ResultsThe gross atherosclerotic lesion area in the aortic arch increased by 15.3% in high-fat-diet rabbits exposed to TSST-1 compared to that in the control group. In the atherosclerotic lesions, TSST-1 exposure increased the content of smooth muscle cells. Moreover, TSST-1 treatment up-regulated serum tumor necrosis factor alpha (TNF-α) level, but did not affect serum lipids (except for triglycerides) and endotoxin in the rabbits.ConclusionsOur data validated that chronic stimulation with TSST-1 facilitates the progression of atherosclerosis in rabbits independently of endotoxins, indicating that S. aureus and its SAgs may be targets to prevent and treat atherosclerosis.

| S-EPMC6933490 | biostudies-literature

Staphylococcus aureus Superantigen-Like Protein SSL1: A Toxic Protease.

Project description:Staphylococcus aureus is a major cause of corneal infections that can cause reduced vision, even blindness. Secreted toxins cause tissue damage and inflammation resulting in scars that lead to vision loss. Identifying tissue damaging proteins is a prerequisite to limiting these harmful reactions. The present study characterized a previously unrecognized S. aureus toxin. This secreted toxin was purified from strain Newman ?hla?hlg, the N-terminal sequence determined, the gene cloned, and the purified recombinant protein was tested in the rabbit cornea. The virulence of a toxin deletion mutant was compared to its parent and the mutant after gene restoration (rescue strain). The toxin (23 kDa) had an N-terminal sequence matching the Newman superantigen-like protein SSL1. An SSL1 homodimer (46 kDa) had proteolytic activity as demonstrated by zymography and cleavage of a synthetic substrate, collagens, and cytokines (IL-17A, IFN-?, and IL-8); the protease was susceptible to serine protease inhibitors. As compared to the parent and rescue strains, the ssl1 mutant had significantly reduced virulence, but not reduced bacterial growth, in vivo. The ocular isolates tested had the ssl1 gene, with allele type 2 being the predominant type. SSL1 is a protease with corneal virulence and activity on host defense and structural proteins.

| S-EPMC6471365 | biostudies-literature

Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300 Staphylococcus aureus.

Project description:Staphylococcus aureus is a leading infectious cause of life-threatening disease in humans, yet there is currently no vaccine to combat this bacterium. The pathogenesis of S. aureus is mediated by a diverse array of protein toxins including a large family of secreted pyrogenic superantigens. Neutralization of superantigens, including SEB and TSST-1, has proven to be protective in several animal models of toxic shock and sepsis. We demonstrate, for the first time, that a far more prevalent staphylococcal superantigen, SEK, can also induce lethal shock in mice. Additionally, we describe monoclonal antibodies (mAbs) that inhibit SEK-induced mitogenicity as well as protect against SEK-induced lethality, and enhance survival from S. aureus septicemia in murine models. MAb-4G3 (IgG2b), mAb-5G2 (IgG1), and mAb-9H2 (IgG1), all inhibit SEK-induced proliferation and cytokine production of human immune cells. We then demonstrate that passive immunization with a combination of mAb-4G3 and mAb-5G4, 2 mAbs that do not compete for epitope(s) on SEK, significantly enhance survival in a murine model of SEK-induced toxic shock (p = 0.006). In the setting of sepsis, passive immunization with this combination of mAbs also significantly enhances survival in mice after challenge with CA-MRSA strain USA300 (p = 0.03). Furthermore, septic mice that received mAb treatment in conjunction with vancomycin exhibit less morbidity than mice treated with vancomycin alone. Taken together, these findings suggest that the contribution of SEK to S. aureus pathogenesis may be greater than previously appreciated, and that adjunctive therapy with passive immunotherapy against SEs may be beneficial.

| S-EPMC5626247 | biostudies-literature

Staphylococcal superantigen-like protein 10 enhances the amyloidogenic biofilm formation in Staphylococcus aureus.

Project description:Staphylococcus aureus is a highly infectious pathogen that represents a significant burden on the current healthcare system. Bacterial attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in chronic diseases such as endocarditis, osteomyelitis and wound infections. These biofilms decrease bacterial susceptibility to antibiotics and immune defences, making the infections challenging to treatment. S. aureus produces numerous exotoxins that contribute to the pathogenesis of the bacteria. In this study, we have identified a novel function of staphylococcal superantigen-like protein 10 (SSL10) in enhancing the formation of staphylococcal biofilms. Biofilm biomass is significantly increased when SSL10 is added exogenously to bacterial cultures, whereas SSL2 and SSL12 are found to be less active. Exogenously added SSL10 mask the surface charge of the bacterial cells and lowers their zeta potential, leading to the aggregation of the cells. Moreover, the biofilm formation by SSL10 is governed by amyloid aggregation, as evident from spectroscopic and microscopic studies. These findings thereby give the first overview of the SSL-mediated amyloid-based biofilm formation and further drive the future research in identifying potential molecules for developing new antibacterial therapies against Staphylococcus aureus.

| S-EPMC10701973 | biostudies-literature

Carriage of the Toxic Shock Syndrome Toxin Gene by Contemporary Community-Associated Staphylococcus aureus Isolates.

Project description:We report here the prevalence of the tst-1 gene among 252 methicillin-susceptible Staphylococcus aureus (MSSA) isolates and 458 methicillin-resistant S aureus (MRSA) isolates collected from 531 subjects between 2008 and 2017, one of which was recovered from a child with MRSA toxic shock syndrome. tst-1 was encoded by 43 (6%) S aureus isolates overall: 42 (16.7%) MSSA isolates and 1 (0.2%) MRSA isolate (P < .001).

| S-EPMC6831934 | biostudies-literature

The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function.

Project description:Staphylococcus aureus infective endocarditis (IE) is a fast-progressing and tissue-destructive infection of the cardiac endothelium. The superantigens (SAgs) toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin C (SEC), and the toxins encoded by the enterotoxin gene cluster (egc) play a novel and essential role in the etiology of S. aureus IE. Recent studies indicate that SAgs act at the infection site to cause tissue pathology and promote vegetation growth. The underlying mechanism of SAg involvement has not been clearly defined. In SAg-mediated responses, immune cell priming is considered a primary triggering event leading to endothelial cell activation and altered function. Utilizing immortalized human aortic endothelial cells (iHAECs), we demonstrated that TSST-1 directly activates iHAECs, as documented by upregulation of vascular and intercellular adhesion molecules (VCAM-1 and ICAM-1). TSST-1-mediated activation results in increased monolayer permeability and defects in vascular reendothelialization. Yet stimulation of iHAECs with TSST-1 fails to induce interleukin-8 (IL-8) and IL-6 production. Furthermore, simultaneous stimulation of iHAECs with TSST-1 and lipopolysaccharide (LPS) inhibits LPS-mediated IL-8 and IL-6 secretion, even after pretreatment with either of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-1β. IL-8 suppression is not mediated by TSST-1 binding to its canonical receptor major histocompatibility complex class II (MHC-II), supporting current evidence for a nonhematopoietic interacting site on SAgs. Together, the data suggest that TSST-1 differentially regulates cell-bound and secreted markers of endothelial cell activation that may result in dysregulated innate immune responses during S. aureus IE. Endothelial changes resulting from the action of SAgs can therefore directly contribute to the aggressive nature of S. aureus IE and development of life-threatening complications.

| S-EPMC5820935 | biostudies-literature

Involvement of enterotoxins G and I in staphylococcal toxic shock syndrome and staphylococcal scarlet fever.

Project description:We investigated the involvement of the recently described staphylococcal enterotoxins G and I in toxic shock syndrome. We reexamined Staphylococcus aureus strains isolated from patients with menstrual and nonmenstrual toxic shock syndrome (nine cases) or staphylococcal scarlet fever (three cases). These strains were selected because they produced none of the toxins known to be involved in these syndromes (toxic shock syndrome toxin 1 and enterotoxins A, B, C, and D), enterotoxin E or H, or exfoliative toxin A or B, despite the fact that superantigenic toxins were detected in a CD69-specific flow cytometry assay measuring T-cell activation. Sets of primers specific to the enterotoxin G and I genes (seg and sei, respectively) were designed and used for PCR amplification. All of the strains were positive for seg and sei. Sequence analysis confirmed that the PCR products, corresponded to the target genes. We suggest that staphylococcal enterotoxins G and I may be capable of causing human staphylococcal toxic shock syndrome and staphylococcal scarlet fever.

| S-EPMC85251 | biostudies-literature

New insights into the prevention of staphylococcal infections and toxic shock syndrome.

Project description:Staphylococcus aureus is a major human pathogen capable of causing various diseases, from skin infections to life-threatening pneumonia and toxic shock syndrome. S. aureus exoproteins, including superantigens, contribute significantly to the pathogenesis of this organism. Antibiotics inhibit growth, but often provide no protection from S. aureus exoproteins. With the emergence of antibiotic-resistant S. aureus, new therapeutic options to treat or prevent S. aureus-associated diseases are critical. Most S. aureus infections begin on the skin or mucosal surfaces from direct inflammatory or cytotoxic effects of exotoxins. Therefore, antitoxin therapies that prevent toxin production and prevent their effects on host cells are being researched. Current treatments for staphylococcal diseases and recent developments in antitoxin therapeutic agents and vaccines are reviewed.

| S-EPMC3102526 | biostudies-literature

Local Epidermal Growth Factor Receptor Signaling Mediates the Systemic Pathogenic Effects of Staphylococcus aureus Toxic Shock Syndrome.

Project description:Secreted factors of Staphylococcus aureus can activate host signaling from the epidermal growth factor receptor (EGFR). The superantigen toxic shock syndrome toxin-1 (TSST-1) contributes to mucosal cytokine production through a disintegrin and metalloproteinase (ADAM)-mediated shedding of EGFR ligands and subsequent EGFR activation. The secreted hemolysin, α-toxin, can also induce EGFR signaling and directly interacts with ADAM10, a sheddase of EGFR ligands. The current work explores the role of EGFR signaling in menstrual toxic shock syndrome (mTSS), a disease mediated by TSST-1. The data presented show that TSST-1 and α-toxin induce ADAM- and EGFR-dependent cytokine production from human vaginal epithelial cells. TSST-1 and α-toxin also induce cytokine production from an ex vivo porcine vaginal mucosa (PVM) model. EGFR signaling is responsible for the majority of IL-8 production from PVM in response to secreted toxins and live S. aureus. Finally, data are presented demonstrating that inhibition of EGFR signaling with the EGFR-specific tyrosine kinase inhibitor AG1478 significantly increases survival in a rabbit model of mTSS. These data indicate that EGFR signaling is critical for progression of an S. aureus exotoxin-mediated disease and may represent an attractive host target for therapeutics.

| S-EPMC4944920 | biostudies-literature

Swine methicillin-resistant <i>Staphylococcus aureus</i> carrying toxic-shock syndrome toxin gene in Hong Kong, China.

Project description:We report a SCCmec II, ST39 methicillin-resistant Staphylococcus aureus isolate from pigs that harboured toxic-shock syndrome toxin gene (tsst-1). The gene was located in a rare pathogenicity island SaPI68111, which also carried enterotoxin genes that can cause fatal infections. Pigs may potentially serve as a reservoir for MRSA dissemination.

| S-EPMC7473289 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data