Effect of streptolysin S on mammalian cells

Snyder, Irvin S.; Hamilton, Tom R.

doi:10.1002/path.1700860135

Cited by 6 publications

(6 citation statements)

References 6 publications

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“…Similar data were reported for the cytotoxic effects of other haemolysins (Snyder and Hamilton, 1963;Wiseman, 1968;Thelestam, Mollby and Wadstrom, 1973;Mollby, Thelestam and Wadstrom, 1974). In addition, the dose-response kinetics for 3T3-cell cytotoxicity were similar to those reported for erythrocyte lysis by Rennie, Freer, and Arbuthnott (1974).…”

Section: Discussionsupporting

confidence: 83%

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Cytotoxic Activity of Partially Purified Escherichia Coli Alpha Haemolysin

Cavalieri

Snyder

1982

Journal of Medical Microbiology

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SUMMARY. Alpha haemolysin, produced by Escherichia coli, grown in a chemically defined medium, was purified 19-fold and the endotoxin content reduced 2 176-fold by ultrafiltration and glycerol-gradient ultracentrifugation. Immunodiffusion of purified a haemolysin (PH) against antiserum to crude haemolysin (CH) revealed only one precipitation line. PH was cytotoxic in nanogram amounts for mouse-fibroblast 3T3 cells, and the cytotoxicity exhibited proportional dose-response and time-course kinetics. The cytotoxic and haemolytic activities of PH were neutralised by immunoglobulins to CH. A mutant, produced by treating the haemolytic wild type with mitomycin C, possessed all of the biochemical characteristics of the wild type with the exception that the extracellular products of the mutant were non-haemolytic and noncyto toxic.

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Section: Discussionsupporting

confidence: 83%

“…As little as 10 HU50 (23 ng of protein) of PH killed 90% or 4.3 x lo5 3T3 cells and even 2 HU50 showed significant killing. By comparison, 10 HU of streptolysin S is the minimum amount that kills lo5 McCoy cells, with as little as 0.5 HU reducing the viable cell counts to 25% of control values (Snyder and Hamilton, 1963).…”

Section: Discussionmentioning

confidence: 98%

Cytotoxic Activity of Partially Purified Escherichia Coli Alpha Haemolysin

Cavalieri

Snyder

1982

Journal of Medical Microbiology

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“…In addition, our data demonstrate a cytotoxic effect that is directly attributable to SLS. Earlier reports demonstrating more complete cell lysis after incubation with purified SLS presumably reflect peptide concentrations significantly higher than those produced by GAS in vitro (28,39).…”

Section: Discussionmentioning

confidence: 89%

“…In some instances, the molecule effecting cell lysis was concluded to be SLS, since the cell injury could be inhibited by SLS antagonists and because GAS naturally deficient in SLS production produced little or no cell damage (28). The use of purified protein preparations also supported SLS cytotoxicity but in addition indicated that SLO mediated a similar effect (16,28,39). The conclusions from these early studies and their relevance to human infection were limited either by the inability to control for the expression of confounding cytotoxins by GAS or by the use of potentially supraphysiological concentrations of purified protein.…”

Section: Discussionmentioning

confidence: 94%

Cytotoxic Effects of Streptolysin O and Streptolysin S Enhance the Virulence of Poorly Encapsulated Group A Streptococci

et al. 2003

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Although the toxicity of streptolysin O (SLO) and streptolysin S (SLS) in purified group A streptococci (GAS) has been established, the effect of these molecules in natural infection is not well understood. To identify whether biologically relevant concentrations of SLO and SLS were cytotoxic to epithelial and phagocytic cells that the bacteria would typically encounter during human infection and to characterize the influence of cell injury on bacterial pathogenesis, we derived GAS strains deficient in SLO or SLS in the background of an invasive GAS M3 isolate and determined their virulence in in vitro and in vivo models of human disease. Whereas bacterial production of SLO resulted in lysis of both human keratinocytes and polymorphonuclear leukocytes, GAS expression of SLS was associated only with keratinocyte injury. Expression of SLO but not SLS impaired polymorphonuclear leukocyte killing of GAS in vitro, but this effect could only be demonstrated in the background of acapsular organisms. In mouse invasive soft-tissue infection, neither SLO or SLS expression significantly influenced mouse survival. By contrast, in a mouse model of bacterial sepsis after intraperitoneal inoculation of GAS, SLO expression enhanced the virulence of both encapsulated and acapsular GAS, whereas SLS expression increased the virulence only of acapsular GAS. We conclude that the cytotoxic effects of SLO protect GAS from phagocytic killing and enhance bacterial virulence, particularly of strains that may be relatively deficient in hyaluronic acid capsule. Compared to SLO, SLS in this strain background has a more modest influence on GAS pathogenicity and the effect does not appear to involve bacterial resistance to phagocytosis.Group A streptococci (GAS) are important human pathogens. Millions of children each year develop GAS pharyngitis. Although throat infection is typically benign, it can be complicated by the development of acute and chronic rheumatic heart disease. Invasive GAS infection occurs less frequently than pharyngitis but causes significantly more morbidity. The incidence of severe invasive GAS disease associated with shock and organ failure appears to be increasing (14,38,40).GAS produce two hemolysins that may contribute to pathogenesis. Streptolysin O (SLO) is a well-characterized oxygenlabile prototype of a cholesterol-binding bacterial exotoxin. When cultured in broth, GAS express SLO during exponentialphase and early stationary-phase growth (1). Streptolysin S (SLS) is an oxygen-stable oligopeptide primarily responsible for the characteristic zone of beta-hemolysis surrounding GAS colonies grown on blood-agar medium (17). SLS production occurs when cells are in stationary-phase growth conditions in broth culture (9).Early studies of purified SLO and SLS demonstrated that these hemolysins were toxic to a variety of human cells in vitro and in vivo (3,10,16,19,20). In rabbits, injection of SLO caused blood vessel contraction, increased capillary permeability, massive intravascular thrombosis, dermal necrosis, cardio...

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“…The hemolytic and cytotoxic properties of streptococcal filtrates have been shown to be associated with two extracellular hemolytic substances: streptolysin 0 and streptolysin S (3,5,11,14,18,19,21,26,28,30). Whereas streptolysin 0 is an immunogenic, SH-dependent protein (18,19,28), streptolysin S is nonimmunogenic and is considered to be a complex between nonspecific carrier molecules (ribonucleic acid [RNA], albumin, alpha-lipoprotein, Tween, Triton, trypan blue, etc.)…”

mentioning

confidence: 99%

Oxygen-Stable Hemolysins of Group A Streptococci VIII. Leukotoxic and Antiphagocytic Effects of Streptolysins S and O

1972

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Streptolysin S exists in a cell-bound form and as an extracellular complex between a nonspecific carrier (serum, serum albumin, ribonucleic acid [RNA], Triton, Tween) and a hemolytic moiety (probably a peptide) synthesized by streptococci. Although all the forms of streptolysin S, at 100 hemolytic units, killed mouse leukocyte monolayers, the time needed to kill 100% of the cells varied with the different streptolysin S preparations. Whereas 30 min was sufficient for the cell-bound hemolysin to kill all of the cells, 60 and 180 min were required when RNA streptolysin S and serum streptolysin S, respectively, were employed. Addition of 10% mouse serum to RNA streptolysin S or to cell-bound hemolysin delayed the killing of the leukocytes. The delayed killing observed with serum and albumin hemolysins is probably due to competition for the hemolytic moiety between the carrier molecules and target sites (phospholipids) upon the leukocyte membrane. Serum streptolysin S must

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Effect of streptolysin S on mammalian cells

Cited by 6 publications

References 6 publications

Cytotoxic Activity of Partially Purified Escherichia Coli Alpha Haemolysin

Cytotoxic Activity of Partially Purified Escherichia Coli Alpha Haemolysin

Cytotoxic Effects of Streptolysin O and Streptolysin S Enhance the Virulence of Poorly Encapsulated Group A Streptococci

Oxygen-Stable Hemolysins of Group A Streptococci VIII. Leukotoxic and Antiphagocytic Effects of Streptolysins S and O

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