Serotype, Biotype, Pyrogenic Exotoxin, Streptolysin O and Exoenzyme Patterns of Invasive Streptococcus pyogenes Isolates from Patients with Toxin Shock Syndrome, Bacteremia and Other Severe Infections

Müller‐Alouf, Heide; Geoffroy, C; Geslin, P.; Bouvet, Anne; Felten, A; Günther, Elisabeth; Ozegowski, Jörg‐Hermann; Reichardt, Werner; Alouf, Joseph E.

doi:10.1007/978-1-4899-1825-3_58

Cited by 14 publications

(18 citation statements)

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“…Studies addressing the role of SpeB in clinical disease have also generated different results. Some studies indicated that increased SpeB production correlated with the more severe form of invasive infections, others found no difference, and still others reported an inverse relation between SpeB production and disease severity (9,29,31,40,43). The majority of these studies included mixtures of GAS serotypes; therefore, differences in SpeB expression among different serotypes or among different subtypes of the same serotype may have masked significant correlations between SpeB expression or level of SpeB production and disease severity.…”

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confidence: 99%

Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases

et al. 2000

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The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases. The expression and amount of the 28-kDa SpeB protein produced were determined by quantitative Western blotting, and protease activity was measured by a fluorescent enzymatic assay. A high degree of variation in SpeB expression was seen among the isolates, and this variation seemed to correlate with the severity and/or clinical manifestation of the invasive infection. The mean amount of 28-kDa SpeB protein and cysteine protease activity produced by isolates from nonsevere cases was significantly higher than that from STSS cases (P ‫؍‬ 0.001). This difference was partly due to the fact that 41% of STSS isolates produced little or no SpeB compared to only 14% of isolates recovered in nonsevere cases. Moreover, the cysteine protease activity among those isolates that expressed SpeB was significantly lower for STSS isolates than for isolates from nonsevere cases (P ‫؍‬ 0.001). Increased SpeB production was also inversely correlated with intact M protein expression, and inhibition of cysteine protease activity blocked the cleavage of the surface M protein. Together, the data support the existence of both an "on-off" and a posttranslational regulatory mechanism(s) controlling SpeB production, and they suggest that isolates with the speB gene in the "off" state are more likely to spare the surface M protein and to be isolated from cases of severe rather than nonsevere invasive infection. These findings may have important implications for the role of SpeB in hostpathogen interactions via regulation of the expression of GAS virulence genes and the severity of invasive disease.

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Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases

et al. 2000

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“…The mitogenic activity of the SAgs tested was evaluated by a lymphocyte proliferation assay on human PBMC as previously described (29). Half-maximal proliferation (10,000 cpm) in response to the purified SMEZ was observed at a concentration of 100 pg/ml, in comparison to 1.8 ng/ml for SPEA (data not shown).…”

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Pyrogenicity and Cytokine-Inducing Properties ofStreptococcus pyogenesSuperantigens: Comparative Study of Streptococcal Mitogenic Exotoxin Z and Pyrogenic Exotoxin A

et al. 2001

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Streptococcal mitogenic exotoxin Z (SMEZ), a superantigen derived from Streptococcus pyogenes, provoked expansion of human lymphocytes expressing the V␤ 2, 4, 7 and 8 motifs of T-cell receptor. SMEZ was pyrogenic in rabbits and stimulated the expression of the T-cell activation markers CD69 and cutaneous lymphocyteassociated antigen. A variety of cytokines was released by human mononuclear leukocytes stimulated with SMEZ, which was 10-fold more active than streptococcal pyrogenic exotoxin A. Th2-derived cytokines were elicited only by superantigens and not by streptococcal cells.Group A streptococci (Streptococcus pyogenes) provoke a wide spectrum of diseases ranging from skin infections and pharyngitis to more severe diseases such as scarlet fever, deep tissue infections, streptococcal toxic shock syndrome (STSS), and probably chronic diseases such as Kawasaki syndrome and guttate psoriasis (1,2,22,23,31,33,44). Several lines of evidence suggest that these diseases are at least partially mediated by extracellular mitogens that belong to the family of the superantigens (SAgs) (2, 33, 47). These effectors trigger polyclonal expansion of T lymphocytes by simultaneous binding to major histocompatibility complex class II molecules on antigen-presenting cells and T-cell receptor via its V␤ domain (37). The V␤ motifs recognized vary from one SAg to another (7). This process leads to the release of high levels of cytokines by antigen-presenting cells and lymphocytes as widely investigated for streptococcal SAgs (6,8,11,12,16,[26][27][28]34,35,41,42). Cytokine accumulation in vivo results in acute shock and other disorders (16,19,20,41,47). In this respect, significant levels of SAg (43) and cytokines in the biological fluids were detected in patients with STSS (6,11,20,32,36,43).S. pyogenes SAgs comprise the classical erythrogenic (pyrogenic) exotoxins A and C (SPEA and SPEC), encoded by bacteriophage speA and speC genes (2, 31); other novel SAgs (2,17,25,33,34,38,46); and the streptococcal mitogenic exotoxin Z (SMEZ) (3, 18, 38), encoded by the gene smez, which displays 24 allelic forms (39). Four newly discovered genes speG, speH, speJ, and smez-2, were identified (reference 38 and genomic database at Oklahoma University [www .genome.ou.edu/strep.html]). Their corresponding recombinant proteins were highly mitogenic for human peripheral blood mononuclear cells (PBMC). We describe here some immunological and biological properties of a potent mitogen released in the culture supernatant of an S. pyogenes strain (strain L) lacking both speA and speC genes, isolated from a French patient with STSS. This strain was selected among a number of speA-and speC-lacking isolates (40). The mitogen was identified as an SAg corresponding to SMEZ. The pyrogenic and superantigenic properties and the cytokine and skin homing antigen-inducing capacities of SMEZ were investigated in parallel with those of purified SPEA (10) used as a control. The cytokine response of PBMC challenged with heatkilled streptococci was also studied for compa...

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“…pUC18 and plasmid pCCY12 containing the intact ypmA gene were introduced into superantigen-deficient Y. pseudotuberculosis H194 by electroporation. T-cell proliferation induced by overnight culture supernatants was measured by [ 3 H]thymidine incorporation (34). Each column represents the average of three values Ϯ SD.…”

Section: Discussionmentioning

confidence: 99%

“…Lymphocyte proliferation tests were performed on human peripheral blood mononuclear cells (PBMC) as previously described (34). Briefly, PBMC were separated from healthy-donor whole blood by Ficoll-gradient centrifugation, and 10 6 cells were cultivated in Eagle medium supplemented with gentamicin (8 g/ml), L-glutamine (2 mM), and inactivated calf serum (20%) in the presence of an overnight culture supernatant from Y. pseudotuberculosis.…”

Section: Methodsmentioning

confidence: 99%

Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosisin Mice

et al. 2000

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The gram-negative bacterium Yersinia pseudotuberculosis is widely spread in nature and is responsible for sporadic infection in many animal species (10). Humans are commonly infected after ingestion of food or water contaminated with excreta of infected animals. Y. pseudotuberculosis causes acute ileitis and mesenteric lymphadenitis, sometimes complicated by septicemia (10, 26), but is also responsible for the occurrence of postinfection complications such as reactive arthritis and erythema nodosum (10,35,45,46). This microorganism has been suggested as one of the causative agents of Kawasaki syndrome, an acute, self-limited vasculitis affecting predominantly infants and young children (4,25,39). A few years ago, Y. pseudotuberculosis strains producing a mitogen activity were isolated from a mass outbreak in Japan (48) and from a patient with Kawasaki-like symptoms (1, 51). The substance, purified from bacterial lysates and exhibiting a mitogenic activity on human peripheral blood mononuclear cells (PBMC), was first designated YPM, for Y. pseudotuberculosis-derived mitogen (30), and then YPMa after the discovery of a variant (36). YPMa was characterized as a 14.5-kDa superantigenic toxin activating human T lymphocytes bearing T-cell receptors exhibiting the V␤3, V␤9, V␤13.1, and V␤13.2 variable regions (1, 48). The geographic distribution of the 456-bp superantigenencoding gene ypmA is rather heterogeneous, being present in most Y. pseudotuberculosis strains from the Far East but only in about 20% of European clinical isolates (13,52).A recent study showed that 61% of patients acutely infected with Y. pseudotuberculosis, especially those with systemic complications, had elevated anti-YPM immunoglobulin G level in blood, thereby demonstrating the production of YPMa in vivo (2). Furthermore, V␤3-bearing T cells were increased in patients during the acute phase of the disease (2). Additionally, Miyoshi-Akiyama et al. (32) found that purified YPMa was able to induce lethal shock in a murine experimental model, demonstrating the toxicity of the Y. pseudotuberculosis superantigenic toxin in vivo. The toxin was also found to alter in vitro epithelial function by reducing active ion transport and increasing epithelial permeability (16). Altogether, these data suggest a role of YPMa in the pathogenesis of Y. pseudotuberculosis infections, but experimental evidence necessary to confirm this hypothesis is lacking. In this study, we constructed a superantigen-deficient mutant of Y. pseudotuberculosis and tested its virulence in a mouse experimental model of infection. Rodents have been extensively used as the animal model to study Yersinia infections since they develop a disease resembling yersiniosis in humans (22). We found that inactivation of ypmA reduced the virulence of Y. pseudotuberculosis after intravenous (i.v.) challenge but not after intragastric (i.g.) inoculation, demonstrating an exacerbated toxicity of YPMa-producing Y. pseudotuberculosis in systemic infection. MATERIALS AND METHODSBacterial strains, growth ...

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Serotype, Biotype, Pyrogenic Exotoxin, Streptolysin O and Exoenzyme Patterns of Invasive Streptococcus pyogenes Isolates from Patients with Toxin Shock Syndrome, Bacteremia and Other Severe Infections

Cited by 14 publications

References 4 publications

Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases

Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases

Pyrogenicity and Cytokine-Inducing Properties ofStreptococcus pyogenesSuperantigens: Comparative Study of Streptococcal Mitogenic Exotoxin Z and Pyrogenic Exotoxin A

Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosisin Mice

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