Cloning, characterization and overexpression of a <i>Streptococcus pyogenes</i> gene encoding a new type of mitogenic factor

Iwasaki, Makoto; Igarashi, Hisanaga; Hinuma, Yorio; Yutsudo, Takashi

doi:10.1016/0014-5793(93)80323-m

Cited by 64 publications

(44 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequences specific for speA (32), speB (34), speC (24), speF (28), speG (56), speH (56), speJ (56), smeZ (21), ssa (59), cpa (55), cpa-1 (T. Miyoshi-Akiyama, N. Wakisaka, J. Zhao, and T. Uchiyama, unpublished data), fba (75), fbp-54 (Miyoshi-Akiyama et al, unpublished), pfbp (61), prtf-1 (66), prtf-2 (29), prtf-15 (35), sciA (58), sciB (78), sfb (72), and sfb-II (40) were detected by PCR on a model 9600 thermocycler (Perkin-Elmer, Gouda, The Netherlands) with the primers listed in Table 1. Amplification of all genes was carried out under the following conditions: an initial 5-min denaturation step at 96°C, followed by 30 cycles of denaturation at Table 1, and 70 s of extension at 72°C, with a final extension step at 72°C for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Site-Specific Manifestations of Invasive Group A Streptococcal Disease: Type Distribution and Corresponding Patterns of Virulence Determinants

Vlaminckx¹,

Mascini²,

Schellekens

et al. 2003

J Clin Microbiol

View full text Add to dashboard Cite

As part of a national surveillance program on invasive group A streptococci (GAS), isolates that caused specific manifestations of invasive GAS disease in The Netherlands were collected between 1992 and 1996. These site-specific GAS infections involved meningitis, arthritis, necrotizing fasciitis, and puerperal sepsis. An evaluation was performed to determine whether GAS virulence factors correlate with these different disease manifestations. PCRs were developed to detect 9 genes encoding exotoxins and 12 genes encoding fibronectin binding proteins. The genetic backgrounds of all isolates were determined by M genotyping and pulsed-field gel electrophoresis (PFGE) analysis. The predominant M types included M1, M2, M3, M4, M6, M9, M12, and M28. Most M types were associated with all manifestations of GAS disease. However, M2 was found exclusively in patients with puerperal sepsis, M6 predominated in patients with meningitis, and M12 predominated in patients with GAS arthritis. While characteristic gene profiles were detected in most M types, the resolution of detection of different gene profiles within M genotypes was enhanced by PFGE analysis, which clearly demonstrated the existence of some clonal lineages among invasive GAS isolates in The Netherlands. M1 isolates comprised a single clone carrying highly mitogenic toxin genes (speA, smeZ) and were associated with toxic shock-like syndrome. Toxin profiles were highly conserved among the most virulent strains, such as M1 and M3.

show abstract

Section: Methodsmentioning

confidence: 99%

Site-Specific Manifestations of Invasive Group A Streptococcal Disease: Type Distribution and Corresponding Patterns of Virulence Determinants

Vlaminckx¹,

Mascini²,

Schellekens

et al. 2003

J Clin Microbiol

View full text Add to dashboard Cite

show abstract

“…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]).…”

mentioning

confidence: 99%

“…Polymyxin B did not affect temperature eleva- tion, confirming that the purified SAg is pyrogenic per se. To our knowledge, the pyrogenicities of other recently described SAgs such as mitogenic factor/SPEF (17,34,46), SSA (25), SMEZ (18), and SPEG, SPEH, and SMEZ-2 (38) have not been investigated. SMEZ preparation was assessed for its ability to stimulate in vitro expression by target cells of the skin-selective lymphocyte homing receptor known as cutaneous lymphocyte-associated antigen (CLA) as already established for other staphylococcal and streptococcal SAgs (21,49,50).…”

mentioning

confidence: 99%

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

et al. 2001

View full text Add to dashboard Cite

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...

show abstract

“…PCR amplicons specific for the streptococcal superantigen exotoxins SpeA, SpeB, SpeC, SpeF, SpeG, SpeH, SpeI, SpeJ, SmeZ/2 and SSA were detected with AmpliTaq Gold (Applied Biosystems). The PCR primers used in this study were based on previously published sequences (11,13,17,19). Samples were placed in a GeneAmp PCR System 9700 thermocycler (Applied Biosystems), and the following cycle parameters were used: preincubation at 95°C for 10 min; 30 cycles of 94°C for 30 s, 50°C for 30 s, and 72°C for 1 min; and a final extension at 72°C for 5 min.…”

mentioning

confidence: 99%

Fatal Case of Toxic Shock-Like Syndrome Due to Group C Streptococcus Associated with Superantigen Exotoxin

et al. 2004

View full text Add to dashboard Cite

Group C streptococci have been reported to cause invasive disease similar to that classically associated with group A streptococcus (GAS). We describe a fatal case of toxic shock-like syndrome due to Streptococcus equi subsp. zooepidemicus. The causative organism did not possess any known GAS superantigen exotoxin genes but did show evidence of superantigen production. CASE REPORTA 63-year-old man developed left thigh pain and swelling while on an airplane flight. Two hours later, he developed fever, rigors, and a rapidly progressing skin rash on his trunk and limbs. Two days earlier, after presenting with vertigo and vomiting, he had received an intramuscular injection of prochlorperazine into the left thigh for presumed acute labyrinthitis.Treatment was commenced for presumed meningococcal sepsis with intravenous (i.v.) benzylpenicillin and ceftriaxone at his local hospital. A cranial computerized tomography scan showed no abnormalities. He was intubated for a reduced conscious state and transferred to the intensive care unit at our institution.Examination revealed a temperature 39.5°C, a pulse of 120/ min, a blood pressure of 100/60 mmHg, and a confluent erythematous skin rash on his trunk and limbs, with petechiae on his legs. His left thigh was tender, swollen, and erythematous. Hypotension developed requiring inotropic support, and there were no other clinical features of toxic shock syndrome (TSS).Initial investigations revealed a leukocyte count of 5.1 ϫ 10 9 /liter (61% neutrophils, 18% band neutrophils) and a platelet count of 25 ϫ 10 9 /liter; the blood film showed neutrophilia with a left shift and toxic granulations. The C-reactive protein level was 239 mg/liter (normal range, Ͻ5 mg/liter). Serum urea was 12.8 mmol/liter (normal range, 2.5 to 9.6 mmol/liter), creatinine was 194 mol/liter (normal range, 40 to 120 mol/ liter), calcium was 1.84 mmol/liter (normal range, 2.2 to 2.6 mmol/liter), and lactate was 9. An ultrasound scan revealed generalized edema of the anterolateral musculature of the left thigh with no abscess. At operation, there was marked subcutaneous and muscle edema but no obvious necrosis. Biopsies demonstrated muscle necrosis and gram-positive cocci. Treatment was continued for presumed group A streptococcus-associated soft-tissue infection and TSS with benzylpenicillin and clindamycin plus i.v. immunoglobulin (IVIG) at 1.5 g/kg.Postoperatively, he had a persistent fever exceeding 40°C and developed progressive multisystem organ failure. Repeat hemoglobin was 7.9 g/dl, leukocytes were 26.0 ϫ 10 9 /liter, and platelets were 14 ϫ 10 9 /liter. He had circulatory failure, requiring high-dose i.v. adrenaline and noradrenaline infusions, and ventricular tachycardia, requiring cardioversion. A transthoracic echocardiogram revealed severe global hypokinesis with no evidence of endocarditis. Respiratory failure developed with increasing hypoxia and ventilatory requirements. Chest radiograph revealed bilateral diffuse pulmonary alveolar opacities. Anuric renal failure (serum creatinine, 402 m...

show abstract

Cloning, characterization and overexpression of a Streptococcus pyogenes gene encoding a new type of mitogenic factor

Cited by 64 publications

References 23 publications

Site-Specific Manifestations of Invasive Group A Streptococcal Disease: Type Distribution and Corresponding Patterns of Virulence Determinants

Site-Specific Manifestations of Invasive Group A Streptococcal Disease: Type Distribution and Corresponding Patterns of Virulence Determinants

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

Fatal Case of Toxic Shock-Like Syndrome Due to Group C Streptococcus Associated with Superantigen Exotoxin

Contact Info

Product

Resources

About