scholarly journals Staphylococcal Enterotoxin C Subtypes Are Differentially Associated with Human Infections and Immunobiological Activities

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Olivia N. Chuang-Smith ◽  
Patrick M. Schlievert
Keyword(s):  
Virulence Factors ◽  
Toxic Shock Syndrome ◽  
Mononuclear Cells ◽  
Rabbit Model ◽  
Purpura Fulminans ◽  
Staphylococcal Enterotoxin ◽  
Thymidine Uptake ◽  
Toxic Shock ◽  
Content Type ◽  
Hemorrhagic Pneumonia

ABSTRACT Staphylococcus aureus causes significant infections, responsible for toxic shock syndrome (TSS), hemorrhagic pneumonia, and many other infections. S. aureus secretes virulence factors, which include superantigens such as staphylococcal enterotoxins (SEs). We examined differences in immunobiological activities and disease associations among the four human SEC subtypes. We sequenced the sec gene from 35 human isolates to determine SEC subtypes. Upon finding differences in disease association, we used a [3H]thymidine uptake assay to examine SEC-induced superantigenicity. We also employed a rabbit model of SEC-induced TSS. SEC-2 and SEC-3 were associated with menstrual TSS and vaginal isolates from healthy women, whereas SEC-4 was produced by USA400 isolates causing purpura fulminans and hemorrhagic pneumonia. SEC subtypes differed in potency in a TSS rabbit model and in superantigenicity. There was no difference in superantigenicity when tested on human peripheral blood mononuclear cells. Despite differences, all SECs reacted with polyclonal antibodies raised against the other SEC subtypes. The associations of SEC subtypes with different infections suggest that S. aureus produces virulence factors according to host niches. IMPORTANCE Staphylococcal enterotoxin C has four subtypes that cause human diseases, designated SEC-1 to -4. This study shows that SEC-2 and SEC-3 are the most toxic subtypes in a rabbit model and are associated with human vaginal infections or colonization in association with another superantigen, toxic shock syndrome toxin 1. SEC-4 is associated with purpura fulminans and hemorrhagic pneumonia. SEC-1 is uncommon. The data suggest that there is some selective pressure for the SEC subtypes to be associated with certain human niches.

scholarly journals Staphylococcal Superantigens Stimulate Epithelial Cells through CD40 To Produce Chemokines

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Patrick M. Schlievert ◽  
Michael P. Cahill ◽  
Bruce S. Hostager ◽  
Amanda J. Brosnahan ◽  
Aloysius J. Klingelhutz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Toxic Shock Syndrome ◽  
Costimulatory Molecule ◽  
Rabbit Model ◽  
Toxic Shock ◽  
Entire Family ◽  
Chemokine Production ◽  
Content Type ◽  
Vaginal Epithelial Cells

ABSTRACTMucosal and skin tissues form barriers to infection by most bacterial pathogens.Staphylococcus aureuscauses diseases across these barriers in part dependent on the proinflammatory properties of superantigens. We showed, through use of a CRISPR-Cas9 CD40 knockout, that the superantigens toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins (SEs) B and C stimulated chemokine production from human vaginal epithelial cells (HVECs) through human CD40. This response was enhanced by addition of antibodies against CD40 through an unknown mechanism. TSST-1 was better able to stimulate chemokine (IL-8 and MIP-3α) production by HVECs than SEB and SEC, suggesting this is the reason for TSST-1’s exclusive association with menstrual TSS. A mutant of TSST-1, K121A, caused TSS in a rabbit model when administered vaginally but not intravenously, emphasizing the importance of the local vaginal environment. Collectively, our data suggested that superantigens facilitate infections by disruption of mucosal barriers through their binding to CD40, with subsequent expression of chemokines. The chemokines facilitate TSS and possibly other epithelial conditions after attraction of the adaptive immune system to the local environment.IMPORTANCEMenstrual toxic shock syndrome (TSS) is a serious infectious disease associated with vaginal colonization byStaphylococcus aureusproducing the exotoxin TSS toxin 1 (TSST-1). We show that menstrual TSS occurs after TSST-1 interaction with an immune costimulatory molecule called CD40 on the surface of vaginal epithelial cells. Other related toxins, where the entire family is called the superantigen family, bind to CD40, but not with a high-enough apparent affinity to cause TSS; thus, TSST-1 is the only exotoxin superantigen associated. Once the epithelial cells become activated by TSST-1, they produce soluble molecules referred to as chemokines, which in turn facilitate TSST-1 activation of T lymphocytes and macrophages to cause the symptoms of TSS. Identification of small-molecule inhibitors of the interaction of TSST-1 with CD40 may be useful so that they may serve as additives to medical devices, such as tampons and menstrual cups, to reduce the incidence of menstrual TSS.

scholarly journals Temporal and Racial Differences Associated with Atopic Dermatitis Staphylococcus aureus and Encoded Virulence Factors

mSphere ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Joseph A. Merriman ◽  
Elizabeth A. Mueller ◽  
Michael P. Cahill ◽  
Lisa A. Beck ◽  
Amy S. Paller ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Gene Cluster ◽  
Virulence Factors ◽  
Toxic Shock Syndrome ◽  
Enterotoxin Gene ◽  
Toxic Shock ◽  
Gene Encoding ◽  
Content Type ◽  
Toxic Shock Syndrome Toxin

ABSTRACT Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of Staphylococcus aureus toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD) S. aureus isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations. Atopic dermatitis (AD) is an inflammatory skin condition strongly associated with Staphylococcus aureus colonization and infection. S. aureus strains shift in populations in ~10-year intervals depending on virulence factors. Shifts in S. aureus virulence factors may in part explain the racial differences observed in the levels of prevalence and severity of AD. AD S. aureus isolates collected from 2011 to 2014 (103 isolates) and in 2008 (100 isolates) were examined for the prevalence of genes encoding superantigens (SAgs). The strains from 2011 to 2014 were obtained from AD patients as a part of the National Institute of Allergy and Infectious Diseases (NIAID) Atopic Dermatitis Research Network (ADRN). The prevalence of SAg genes was investigated temporally and racially. The enterotoxin gene cluster (EGC) was more prevalent in the 2011–2014 AD isolates than in the 2008 AD isolates. The prevalences of virulence factor genes were similar in European American (EA) and Mexican American (MA) patients but differed in 6 of 22 SAg genes between EA and African American (AA) or MA and AA isolates; notably, AA isolates lacked tstH, the gene encoding toxic shock syndrome toxin 1 (TSST-1). The presence of tstH and sel-p (enterotoxin-like P) was associated with decreased clinical severity and increased blood eosinophils, respectively. The EGC is becoming more prevalent, consistent with the previously observed 10 years of cycling of S. aureus strains. Race-specific S. aureus selection may account for differences in virulence factor profiles. The lack of TSST-1-positive (TSST-1+) AD S. aureus in AA is consistent with the lack of AAs acquiring TSST-1-associated menstrual toxic shock syndrome (TSS). IMPORTANCE Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of Staphylococcus aureus toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD) S. aureus isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations.

A rabbit model of toxic shock syndrome: clinicopathological features

1984 ◽  
Vol 8 (3) ◽  
pp. 205-211 ◽  
Author(s):  
R.J. Arko ◽  
J.K. Rasheed ◽  
C.V. Broome ◽  
F.W. Chandler ◽  
A.L. Paris
Keyword(s):  
Toxic Shock Syndrome ◽  
Rabbit Model ◽  
Clinicopathological Features ◽  
Toxic Shock

Staphylococcus aureusisogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuated virulence in a tampon-associated vaginal infection model of toxic shock syndrome

1999 ◽  
Vol 45 (3) ◽  
pp. 250-256
Author(s):  
Monica L De Boer ◽  
Winnie WS Kum ◽  
Anthony W Chow
Keyword(s):  
Weight Loss ◽  
Toxic Shock Syndrome ◽  
Staphylococcal Enterotoxin ◽  
Aureus Strain ◽  
Infection Model ◽  
Staphylococcal Enterotoxin A ◽  
Toxic Shock ◽  
Vaginal Infection ◽  
Toxic Shock Syndrome Toxin

Since menstrual toxic shock syndrome (MTSS) is associated with a predominant clone of Staphylococcus aureus which produces both toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA), we sought to clarify the role of TSST-1 in a tampon-associated vaginal infection model in New Zealand White (NZW) rabbits, using isogenic tst+/sea+S. aureus mutants in which tst was inactivated by allelic replacement. Rabbits infected with the tst-/sea+strain became ill within 3 days, with fever, weight loss, conjunctival hyperemia, and lethargy. Mortality was significantly higher with the tst+/sea+strain compared to its tst-/sea+isogenic derivative (4/13 vs. 0/14; p < 0.05, Fisher's exact test, 2-tailed). Mean fever index was higher (p < 0.005; t test, 2-tailed) and weight loss more sustained among survivors in the tst+/sea+group. Furthermore, culture filtrates from the tst+/sea+strain induced a significantly greater response in mitogenesis and TNFalpha secretion from rabbit splenocytes in vitro compared to the tst-/sea+isogenic derivative. Thus, regardless of the role of SEA, TSST-1 significantly contributed to both morbidity and mortality in this tampon-associated vaginal infection model in NZW rabbits. This is the first demonstration of the potential role of TSST-1 and SEA in the pathogenesis of MTSS with a MTSS-associated clinical S. aureus strain in a relevant animal model.Key words: toxic-shock syndrome toxin-1, superantigens, rabbit model.

scholarly journals Interleukin-10 (IL-10) Produced by Mutant Toxic Shock Syndrome Toxin 1 Vaccine-Induced Memory T Cells Downregulates IL-17 Production and Abrogates the Protective Effect against Staphylococcus aureus Infection

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Kouji Narita ◽  
Dong-Liang Hu ◽  
Krisana Asano ◽  
Akio Nakane
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Infectious Diseases ◽  
Protective Effect ◽  
Toxic Shock Syndrome ◽  
Long Term Memory ◽  
Toxic Shock ◽  
Content Type ◽  
Memory Phase ◽  
Toxic Shock Syndrome Toxin

ABSTRACT Development of long-term memory is crucial for vaccine-induced adaptive immunity against infectious diseases such as Staphylococcus aureus infection. Toxic shock syndrome toxin 1 (TSST-1), one of the superantigens produced by S. aureus, is a possible vaccine candidate against infectious diseases caused by this pathogen. We previously reported that vaccination with less toxic mutant TSST-1 (mTSST-1) induced T helper 17 (Th17) cells and elicited interleukin-17A (IL-17A)-mediated protection against S. aureus infection 1 week after vaccination. In the present study, we investigated the host immune response induced by mTSST-1 vaccination in the memory phase, 12 weeks after the final vaccination. The protective effect and IL-17A production after vaccination with mTSST-1 were eliminated because of IL-10 production. In the presence of IL-10-neutralizing monoclonal antibody (mAb), IL-17A production was restored in culture supernatants of CD4+ T cells and macrophages sorted from the spleens of vaccinated mice. Vaccinated mice treated with anti-IL-10 mAb were protected against systemic S. aureus infection in the memory phase. From these results, it was suggested that IL-10 produced in the memory phase suppresses the IL-17A-dependent vaccine effect through downregulation of IL-17A production.

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

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Katarina Kulhankova ◽  
Kyle J. Kinney ◽  
Jessica M. Stach ◽  
Françoise A. Gourronc ◽  
Isabella M. Grumbach ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Toxic Shock Syndrome ◽  
Cell Activation ◽  
Current Evidence ◽  
Toxic Shock ◽  
Endothelial Cell Activation ◽  
Content Type ◽  
Toxic Shock Syndrome Toxin ◽  
Stimulation Of ◽  
Aortic Endothelial

ABSTRACTStaphylococcus aureusinfective 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 ofS. aureusIE. 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 duringS. aureusIE. Endothelial changes resulting from the action of SAgs can therefore directly contribute to the aggressive nature ofS. aureusIE and development of life-threatening complications.

Prevalence of Serum Antibody to Staphylococcal Enterotoxin F among Wisconsin Residents: Implications for Toxic-Shock Syndrome

1983 ◽  
Vol 148 (4) ◽  
pp. 692-698 ◽  
Author(s):  
J. M. Vergeront ◽  
S. J. Stolz ◽  
B. A. Crass ◽  
D. B. Nelson ◽  
J. P. Davis ◽  
...  
Keyword(s):  
Toxic Shock Syndrome ◽  
Serum Antibody ◽  
Staphylococcal Enterotoxin ◽  
Toxic Shock

scholarly journals Impact of Currently Marketed Tampons and Menstrual Cups onStaphylococcus aureusGrowth and Toxic Shock Syndrome Toxin 1 ProductionIn Vitro

2018 ◽  
Vol 84 (12) ◽  
pp. e00351-18 ◽  
Author(s):  
Louis Nonfoux ◽  
Myriam Chiaruzzi ◽  
Cédric Badiou ◽  
Jessica Baude ◽  
Anne Tristan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Toxic Shock Syndrome ◽  
Severe Disease ◽  
Toxin Production ◽  
Toxic Shock ◽  
Content Type ◽  
Physiological Conditions ◽  
Simple Protocol ◽  
Toxic Shock Syndrome Toxin ◽  
The Impact

ABSTRACTFifteen currently marketed intravaginal protection products (11 types of tampon and 4 types of menstrual cup) were tested by the modified tampon sac method to determine their effect onStaphylococcus aureusgrowth and toxic shock syndrome toxin 1 (TSST-1) production. Most tampons reducedS. aureusgrowth and TSST-1 production, with differences based on brand and composition, and the level ofS. aureusgrowth was higher in destructured than in unaltered tampons. We observed higher levels ofS. aureusgrowth and toxin production in menstrual cups than in tampons, potentially due to the additional air introduced into the bag by cups, with differences based on cup composition and size.IMPORTANCEMenstrual toxic shock syndrome is a rare but severe disease. It occurs in healthy women vaginally colonized byStaphylococcus aureusproducing toxic shock syndrome toxin 1 using intravaginal protection, such as tampons or menstrual cups. Intravaginal protection induces TSS by the collection of catamenial products, which act as a growth medium forS. aureus. Previous studies evaluated the impact of tampon composition onS. aureusproducing toxic shock syndrome toxin 1, but they are not recent and did not include menstrual cups. This study demonstrates that highly reproducible results forS. aureusgrowth and TSST-1 production can be obtained by using a simple protocol that reproduces the physiological conditions of tampon and cup usage as closely as possible, providing recommendations for tampon or cup use to both manufacturers and consumers. Notably, our results do not show that menstrual cups are safer than tampons and suggest that they require similar precautions.

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