Functional Characterization of Streptococcal Pyrogenic Exotoxin J, a Novel Superantigen

McCormick, John K.; Pragman, Alexa A.; Stolpa, John C.; Leung, Donald Y.M.; Schlievert, Patrick M.

doi:10.1128/iai.69.3.1381-1388.2001

Cited by 46 publications

(35 citation statements)

References 67 publications

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“…Using an isogenic mutant streptococcal strain, deficient in SMEZ production, this work confirms that SMEZ is responsible for all detectable S. pyogenes supernatant-induced TCR V␤8 human T cell proliferation. Streptococcal supernatant from both the parent and smez mutant strain failed to induce detectable expansion of human T cells bearing TCR V␤2, the subset targeted by the recently characterized superantigen SPEJ (18,19), consistent with the low level of residual mitogenicity in the smez mutant strain.…”

Section: Discussionmentioning

confidence: 94%

The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent ofStreptococcus pyogenes

Unnikrishnan

Altmann

Proft

et al. 2002

The Journal of Immunology

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The gene encoding streptococcal mitogenic exotoxin Z (SMEZ) was disrupted in Streptococcus pyogenes. Despite the presence of other superantigen genes, mitogenic responses in human and murine HLA-DQ transgenic cells were abrogated when cells were stimulated with supernatant from the smez− mutant compared with the parent strain. Remarkably, disruption of smez led to a complete inability to elicit cytokine production (TNF-α, lymphotoxin-α, IFN-γ, IL-1 and -8) from human cells, when cocultured with streptococcal supernatants. The potent effects of SMEZ were apparent even though transcription and expression of SMEZ were barely detectable. Human Vβ8+ T cell proliferation in response to S. pyogenes was SMEZ-dependent. Cells from HLA-DQ8 transgenic mice were 3 logs more sensitive to SMEZ-13 than cells from HLA-DR1 transgenic or wild-type mice. In the mouse, SMEZ targeted the human Vβ8+ TCR homologue, murine Vβ11, at the expense of other TCR T cell subsets. Expression of SMEZ did not affect bacterial clearance or survival from peritoneal streptococcal infection in HLA-DQ8 mice, though effects of SMEZ on pharyngeal infection are unknown. Infection did lead to a rise in Vβ11+ T cells in the spleen which was partly reversed by disruption of the smez gene. Most strikingly, a clear rise in murine Vβ4+ cells was seen in mice infected with the smez− mutant S. pyogenes strain, indicating a potential role for SMEZ as a repressor of cognate anti-streptococcal responses.

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Section: Discussionmentioning

confidence: 94%

The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent ofStreptococcus pyogenes

Unnikrishnan

Altmann

Proft

et al. 2002

The Journal of Immunology

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“…The primers used for identification of the spe genes were found in the literature (6,20,27,34,35,42).…”

Section: Methodsmentioning

confidence: 99%

“…In this paper, we present nationwide data on the epidemiology of isolates causing invasive and noninvasive GAS disease prospectively collected during a prolonged period of stable incidence rates. Additionally, we present comparable data for isolates that were identified from either invasive or noninvasive GAS infections as well as from asymptomatic carriers in order to monitor possible trends in the emm distributions; SAg profiles, i.e., the genes encoding pyrogenic exotoxins A to C and F to J, SSA, and SMEZ (speA to speC, speF to speJ, ssa, and smeZ, respectively) (19,27,29,(34)(35)(36)(37); and the hosts' susceptibilities to their own infecting strains.…”

mentioning

confidence: 99%

Variations inemmType among Group A Streptococcal Isolates Causing Invasive or Noninvasive Infections in a Nationwide Study

et al. 2005

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Since the late 1980s several studies have described the increased incidence and severity of invasive group A streptococcal (GAS) infections. However, most studies on GAS pathogenesis have focused on information obtained during outbreaks. We analyzed isolate distribution and host susceptibility as part of a nationwide prospective surveillance study performed between January 2001 and August 2002. GAS isolates collected from 201 patients with invasive infections, 335 patients with noninvasive infections, and 17 asymptomatic carriers were characterized with respect to their emm types and superantigen genotypes. The superantigen-neutralizing capacity and levels of antibodies against streptolysin O and DNAse B were determined for isolates from the sera from 36 invasive cases and 91 noninvasive cases. emm type 1 (emm-1) isolates were significantly more common among invasive cases, whereas emm-4, emm-6, and emm-12 dominated among the noninvasive cases. The distributions of the phage-associated superantigen genes (speA, speC, speH, speI, ssa) differed among invasive and noninvasive isolates, mainly due to their linkage to certain emm types. No significant differences in serum superantigen-neutralizing capacities were observed. The levels of anti-streptolysin O and anti-DNAse B antibodies were highest in the sera from invasive cases. Our study emphasizes the importance of obtaining data during years with stable incidences, which will enable evaluation of future outbreak data.

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“…The primers used for identification of the exotoxin genes were found in the literature (5,25,30,33,34,41). PCR was done as described above.…”

Section: Methodsmentioning

confidence: 99%

Reemergence of emm 1 and a Changed Superantigen Profile for Group A Streptococci Causing Invasive Infections: Results from a Nationwide Study

Ekelund¹,

Skinhøj

Madsen

et al. 2005

J Clin Microbiol

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Between 1999 and 2002, 496 invasive group A streptococcal (GAS) isolates from clinical microbiological departments in Denmark and subsequently 487 (98%) questionnaires from the clinicians treating the patients were received as part of a national surveillance. emm types and streptococcal superantigen (SAg) genes were determined. The incidence of invasive GAS infections was on average 2.3 per 100,000 per year. Bacteremia with no focal symptoms (27%) was together with erysipelas (20%) the most prevalent clinical diagnoses. Streptococcal toxic shock syndrome occurred in 10% of patients, of which 56% died. The overall case fatality rate within 30 days was 23%. In total, 47 different emm types were identified, of which emm1, emm3, emm4, emm12, emm28, and emm89 were identified in 72% of the 493 available isolates. During the 4-year period the presence of emm1 increased from 16% in 1999 to 40% in 2002. Concurrently, the presence of emm3 decreased from 23% in 1999 to 2% in 2002. The emm1 isolates predominantly carried speA, although the frequency decreased from 94% in 1999 to 71% in 2002, whereas the emm1-specific prevalence of speC increased from 25 to 53%. In a historical perspective, this could be interpreted as a reemergence of emm1 and could indicate a possible introduction of a new emm1 subclone. However, this reemergence did not result in any significant changes in the clinical manifestations during the study period. Our results show the complexity of invasive GAS infections, with time-dependent variations in the incidence and distribution of emm and SAg genes, which emphasizes the need for continuous epidemiological and molecular investigations.

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Functional Characterization of Streptococcal Pyrogenic Exotoxin J, a Novel Superantigen

Cited by 46 publications

References 67 publications

The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent ofStreptococcus pyogenes

The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent ofStreptococcus pyogenes

Variations inemmType among Group A Streptococcal Isolates Causing Invasive or Noninvasive Infections in a Nationwide Study

Reemergence of emm 1 and a Changed Superantigen Profile for Group A Streptococci Causing Invasive Infections: Results from a Nationwide Study

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