Kinetics and Regulation of Erythrogenic Toxins Type A and C During Growth of Streptococcus Pyogenes

Ozegowski, Jörg‐Hermann; Wollweber, Leo; Vettermann, Stefan; Müller, Peter-Jürgen; Günther, Elisabeth

doi:10.1016/s0934-8840(96)80061-2

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…Determination of the SpeA expression profile revealed predominant production during the exponential phase (Ozegowski et al ., 1996; Xu and Collins, 1996), which corresponds to the temporal transcription mode of the nra regulator (Podbielski et al ., 1999a) as well as the levels of speA message measured in the nra mutant. While Nra could have a direct effect on speA expression, its influence on transcription of the speB gene and streptolysin S‐encoding sagA / pel genes appears to be more complex.…”

Section: Discussionmentioning

confidence: 99%

The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells

Molinari

Rohde

Talay

et al. 2001

Molecular Microbiology

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Group A streptococci (GAS) specifically attach to and internalize into human epithelial host cells. In some GAS isolates, fibronectin‐binding proteins were identified as being responsible for these virulence traits. In the present study, the previously identified global negative regulator Nra was shown to control the binding of soluble fibronectin probably via regulation of protein F2 and/or SfbII expression in the serotype M49 strain 591. According to results from a conventional invasion assay based on the recovery of viable intracellular bacteria, the increased fibronectin binding did not affect bacterial adherence to HEp‐2 epithelial cells, but was associated with a reduction in the internalization rates. However, when examined by confocal and electron microscopy techniques, the nra‐mutant bacteria were shown to exhibit higher adherence and internalization rates than the corresponding wild type. The mutant bacteria escaped from the phagocytic vacuoles much faster, promoting consistent morphological changes which resulted in severe host cell damage. The apoptotic and lytic processes observed in nra‐mutant infected host cells were correlated with an increased expression of the genes encoding superantigen SpeA, the cysteine protease SpeB, and streptolysin S in the nra‐mutant bacteria. Adherence and internalization rates of a nra/speB‐double mutant at wild‐type levels indicated that the altered speB expression in the nra mutant contributed to the observed changes in both processes. The Nra‐dependent effects on bacterial virulence were confined to infections carried out with stationary growth phase bacteria. In conclusion, the obtained results demonstrated that the global GAS regulator Nra modulates virulence genes, which are involved in host cell damage. Thus, by helping to achieve a critical balance of virulence factor expression that avoids the injury of target cells, Nra may facilitate GAS persistence in a safe intracellular niche.

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Section: Discussionmentioning

confidence: 99%

The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells

Molinari

Rohde

Talay

et al. 2001

Molecular Microbiology

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“…Some investigators reported a direct correlation between logarithmic growth and SPE-A production (16), while others mentioned that SPE-A is produced mainly during the short stationary interphases which interrupt growth (36). In contrast, SPE-B production was detected only when cultures entered the stationary phase (9).…”

Section: Fig 2 Principles Of Competitive Elisa For Spe-a (A)mentioning

confidence: 99%

Invasive and Noninvasive Group A Streptococcal Isolates with DifferentspeAAlleles in The Netherlands: Genetic Relatedness and Production of Pyrogenic Exotoxins A and B

et al. 1999

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Streptococcal pyrogenic exotoxin A (SPE-A) and SPE-B have been implicated in the pathogenesis of severe group A streptococcal (GAS) disease. We studied 31 invasive GAS strains including 18 isolates from patients with toxic shock syndrome and 22 noninvasive strains isolated in The Netherlands between 1994 and 1998. These strains were associated with the different allelic variants of the gene encoding SPE-A. We selected endemic strains with speA-positive M and T serotypes: speA2-associated M1T1 and M22-60T12 strains,speA3-associated M3T3 strains, andspeA4-associated M6T6 strains. SincespeA1-positive isolates were not frequently encountered, we included speA1 strains of different serotypes. The GAS strains were compared genotypically by pulsed-field gel electrophoresis and phenotypically by the in vitro production of SPE-A and SPE-B. All strains within one M and T type appeared to be of clonal origin. Most strains produced SPE-A and SPE-B, but only a minority of thespeA4-positive isolates did so. Among our isolates,speA1- and speA3-positive strains produced significantly more SPE-A than speA2- andspeA4-carrying strains, while SPE-B production was most pronounced among speA1- and speA2-containing strains. There was a marked degree of variability in the amounts of exotoxins produced in vitro by strains that shared the same genetic profile. We conclude that the differences in the in vitro production of SPE-A and SPE-B between our selected strains with identical M and T types were not related to either genetic heterogeneity or the clinical course of GAS disease in the patient from whom they were isolated.

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Influence of the Phosphorylation State on the Biological Activity of a Low-molecular Mitogen from Group A Streptococci

Ozegowski

Günther

Vettermann

et al. 1998

Zentralblatt für Bakteriologie

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Kinetics and Regulation of Erythrogenic Toxins Type A and C During Growth of Streptococcus Pyogenes

Cited by 4 publications

References 30 publications

The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells

The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells

Invasive and Noninvasive Group A Streptococcal Isolates with DifferentspeAAlleles in The Netherlands: Genetic Relatedness and Production of Pyrogenic Exotoxins A and B

Influence of the Phosphorylation State on the Biological Activity of a Low-molecular Mitogen from Group A Streptococci

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