scholarly journals HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS

1960 ◽  
Vol 111 (2) ◽  
pp. 255-284 ◽  
Author(s):  
Dennis W. Watson
Keyword(s):  
Scarlet Fever ◽  
Intravenous Injections ◽  
Streptolysin O ◽  
Bacterial Endotoxins ◽  
Group A ◽  
Shwartzman Reaction ◽  
Host Parasite ◽  
Parasite Factors ◽  
Pyrogenic Activity

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed.

scholarly journals ALTERATIONS IN THE BLOOD COAGULATION SYSTEM INDUCED BY BACTERIAL ENDOTOXIN

1958 ◽  
Vol 107 (3) ◽  
pp. 353-367 ◽  
Author(s):  
Donald G. McKay ◽  
Sandor S. Shapiro
Keyword(s):  
Blood Coagulation ◽  
Marked Decrease ◽  
Fibrinogen Level ◽  
Normal Values ◽  
Bacterial Endotoxin ◽  
Coagulation System ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
The One

The intravenous injection of bacterial endotoxins alter the coagulation system of rabbits' blood in vivo. Twenty-four hours after the first injection the fibrinogen level rises to twice normal values. The second injection at this time causes a 30 to 40 per cent decrease in fibrinogen content in 4 hours. Twenty hours later it again rises to twice normal values. A marked decrease in whole blood coagulation times in silicone occurs 4 hours after both injections but rises to normal values 24 hours following each injection. The circulating platelets drop from average levels of 300,000/c.mm. to 150,000/c.mm. after the first injection. The platelets remain at this low level and decrease to less than 100,000 after the second injection. During this time no fibrinolytic or fibrinogenolytic activity can be detected. Also, there is no significant change in the one stage prothrombin times or antithrombin titres. The marked decrease in circulating fibrinogen at the time when intracapillary thrombi are formed suggests that the "hyaline" thrombi of the generalized Shwartzman reaction are composed, in part, of fibrin. There appears to be a relationship between the level of circulating fibrinogen at the time of injection of bacterial endotoxin and the extent of the thrombosis. The higher the preinjection fibrinogen level, the more extensive is the thrombosis. There is also a relationship between the amount of fibrinogen loss and the extent of thrombosis after the injection. The more extensive the thrombosis the greater is the postinjection decrease in circulating fibrinogen. A comparison between the response of the hemostatic mechanism to tissue thromboplastin and bacterial endotoxin indicates that the latter acts in a unique manner and not by way of a simple "thromboplastic" activity. From the hematological standpoint, "preparation" for the generalized Shwartzman reaction is accompanied by an increased circulating fibrinogen, leukocytosis, and thrombocytopenia.

scholarly journals Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephan Brouwer ◽  
Timothy C. Barnett ◽  
Diane Ly ◽  
Katherine J. Kasper ◽  
David M. P. De Oliveira ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Scarlet Fever ◽  
Global Public Health ◽  
Nasopharyngeal Colonization ◽  
North East ◽  
Streptolysin O ◽  
Knockout Mutants ◽  
Group A ◽  
Bacterial Superantigen

Abstract The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins.

scholarly journals Streptolysin O concentration and activity is central to in vivo phenotype and disease outcome in Group A Streptococcus infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jenny Clarke ◽  
Murielle Baltazar ◽  
Mansoor Alsahag ◽  
Stavros Panagiotou ◽  
Marion Pouget ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Rapid Development ◽  
Clinical Manifestations ◽  
Disease Outcome ◽  
Haemolytic Activity ◽  
Human Pathogens ◽  
Streptolysin O ◽  
Group A

AbstractGroup A Streptoccocus (GAS) is among the most diverse of all human pathogens, responsible for a range of clinical manifestations, from mild superficial infections such as pharyngitis to serious invasive infections such as necrotising fasciitis and sepsis. The drivers of these different disease phenotypes are not known. The GAS cholesterol-dependent cytolysin, Streptolysin O (SLO), has well established cell and tissue destructive activity. We investigated the role of SLO in determining disease outcome in vivo, by using two different clinical lineages; the recently emerged hypervirulent outbreak emm type 32.2 strains, which result in sepsis, and the emm type 1.0 strains which cause septic arthritis. Using clinically relevant in vivo mouse models of sepsis and a novel septic arthritis model, we found that the amount and activity of SLO was vital in determining the course of infection. The emm type 32.2 strain produced large quantities of highly haemolytic SLO that resulted in rapid development of sepsis. By contrast, the reduced concentration and lower haemolytic activity of emm type 1.0 SLO led to translocation of bacteria from blood to joints. Importantly, sepsis associated strains that were attenuated by deletion or inhibition of SLO, then also translocated to the joint, confirming the key role of SLO in determining infection niche. Our findings demonstrate that SLO is key to in vivo phenotype and disease outcome. Careful consideration should be given to novel therapy or vaccination strategies that target SLO. Whilst neutralising SLO activity may reduce severe invasive disease, it has the potential to promote chronic inflammatory conditions such as septic arthritis.

scholarly journals THE PREVENTION OF THE GENERALIZED SHWARTZMAN REACTION WITH SODIUM WARFARIN

1958 ◽  
Vol 107 (3) ◽  
pp. 377-381 ◽  
Author(s):  
Sandor S. Shapiro ◽  
Donald G. McKay
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Control Group ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravascular Coagulation ◽  
Intravenous Injections ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Kidney Liver ◽  
Intravenous Sodium

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis. It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.

scholarly journals Role of NADase in Virulence in Experimental Invasive Group A Streptococcal Infection

2005 ◽  
Vol 73 (10) ◽  
pp. 6562-6566 ◽  
Author(s):  
Angela L. Bricker ◽  
Vincent J. Carey ◽  
Michael R. Wessels
Keyword(s):  
Human Infection ◽  
Host Animal ◽  
Cytotoxic Effects ◽  
Invasive Group ◽  
Streptolysin O ◽  
Group A ◽  
Wild Type Parent

ABSTRACT Group A streptococci (GAS) produce several exoproteins that are thought to contribute to the pathogenesis of human infection. Two such proteins, streptolysin O (SLO) and NAD+-glycohydrolase (NADase), have been shown to interact functionally as a compound signaling toxin. When GAS are bound to the surface of epithelial cells in vitro, SLO forms pores in the cell membrane and delivers NADase to the epithelial cell cytoplasm. In vitro, intoxication of keratinocytes with NADase is associated with cytotoxic effects and induction of apoptosis; however, the importance of NADase during infection of an animal host has not been established. We employed isogenic GAS mutants to assess the contribution of NADase activity to GAS virulence in vivo using mouse models of invasive soft-tissue infection and septicemia. In both models, mutant GAS that lacked NADase activity were significantly attenuated for virulence compared with the isogenic wild-type parent, confirming an important role for NADase in the infection of a host animal. A double mutant lacking SLO and NADase activity had an intermediate virulence phenotype, consistent with the hypothesis that SLO evokes a protective innate immune response. We conclude that NADase and SLO together enhance GAS virulence in vivo.

scholarly journals THE USE OF PRECIPITIN ANALYSIS IN AGAR FOR THE STUDY OF HUMAN STREPTOCOCCAL INFECTIONS

1958 ◽  
Vol 108 (3) ◽  
pp. 385-410 ◽  
Author(s):  
Seymour P. Halbert
Keyword(s):  
Gamma Globulin ◽  
Group A Streptococcus ◽  
Streptococcal Infections ◽  
High Potency ◽  
Streptolysin O ◽  
Combined Use ◽  
Group A ◽  
Human Gamma Globulin ◽  
Human Infections

As evidenced by precipitin analysis with pooled human gamma globulin, at least 12 distinct antigens were produced in cultures by one strain of Group A streptococcus (C203S). It was suggested on this basis, that these antigens were produced in vivo during human infections. By the combined use of continuous flow electrophoresis on paper curtains, and column chromatography with calcium phosphate gels, five of these have been isolated in a probable high state of purity. One of the components was obtained from culture filtrates of a Group C streptococcal strain. Three of the purified antigens have been tentatively identified as streptolysin "O", diphosphopyridinenucleotidase, and proteinase precursor. The latter could be very readily crystallized, and appears "identical" with that described by Elliott. The DPNase was of extremely high potency, 1 mg. being capable of destroying 12.6 gm. of DPN in 7½ minutes at 37°C. The identity of the other two components is uncertain as yet. They are distinct from each other and the above products immunologically, and are not related to the "C" carbohydrate. The applicability of these methods for the analysis of infectious diseases generally was discussed.

scholarly journals THE EFFECTS OF BACTERIAL ENDOTOXIN ON LIPIDE METABOLISM

1959 ◽  
Vol 110 (2) ◽  
pp. 293-309 ◽  
Author(s):  
V. S. LeQuire ◽  
J. D. Hutcherson ◽  
R. L. Hamilton ◽  
M. E. Gray
Keyword(s):  
Total Serum ◽  
Initial Increase ◽  
Total Serum Cholesterol ◽  
Moderate Increase ◽  
Progressive Decrease ◽  
Thorium Dioxide ◽  
Metabolic Alterations ◽  
Intravenous Injections ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction

Single intravenous injections of Shear's polysaccharide in varying dosages invariably produced an elevation in the levels of the total serum lipides 24 hours after injection of endotoxin. The total serum cholesterol and lipide phosphorus were also affected, although they did not change with smaller doses of endotoxin and were rarely elevated to the same degree as were the total serum lipides. The degree of elevation of the serum lipides was apparently related to the amount of endotoxin injected up to a certain point, beyond which there was no further increase. There were two types of response to endotoxin by the serum lipides, a moderate increase and an uncontrolled increase. Higher dosages of endotoxin and fasting apparently increased the incidence of the latter response. No direct correlation could be made between serum lipide responses and histologic evidence typical of the generalized Shwartzman reaction following this regimen of endotoxin injection. The Shwartzman reaction did occur with greater frequency and with lower dosages of endotoxin in fasted animals. Animals given repeated injections of endotoxin showed an initial increase in serum lipides followed by a progressive decrease to normal levels as tolerance to the febrile action of endotoxin appeared. The febrile tolerance as well as the unresponsiveness of the serum lipides to endotoxin was abolished by thorium dioxide (thorotrast) in these animals. In similar experiments a "breakthrough" of lipide unresponsiveness to endotoxin was obtained by increasing the amount of endotoxin injected. Some of the implications of these results for the metabolic alterations produced by bacterial endotoxins are discussed.

scholarly journals ANTIGEN-ANTIBODY REACTION IN THE PATHOGENESIS OF BILATERAL RENAL CORTICAL NECROSIS

1963 ◽  
Vol 117 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Leung Lee
Keyword(s):  
Immune Complexes ◽  
Coagulation System ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Soluble Immune Complexes ◽  
Antigen Antibody ◽  
Glomerular Capillaries

In the presence of reticuloendothelial blockade, the intravenous injection of a protein antigen into specifically immunized rabbits or the infusion of soluble immune complexes into normal animals has been shown to result in the production of bilateral renal cortical necrosis. The similarity in the pathogenesis of this lesion and that seen in the classical generalized Shwartzman reaction produced by bacterial endotoxins is indicated by (a) the failure of both lesions to develop in animals pretreated with large doses of heparin, (b) by the finding of "heparin-precipitable fibrinogen" in the circulation, and (c) by the presence of massive fibrin deposits within the glomerular capillaries. These findings indicate that antigen-antibody reactions in vivo are capable of activating the blood coagulation system and that the mode of action of bacterial endotoxins may have an immunological basis.

scholarly journals STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES

1953 ◽  
Vol 98 (4) ◽  
pp. 331-348 ◽  
Author(s):  
Morgan Berthrong ◽  
Leighton E. Cluff
Keyword(s):  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Buffy Coat ◽  
Single Intravenous Injection ◽  
Bacterial Endotoxins ◽  
Leucocyte Migration ◽  
Shwartzman Reaction ◽  
Local Shwartzman Reaction

Intravenous injection into rabbits of bacterial endotoxins results in an inhibition of migration of leucocytes from the buffy coat of their blood in tissue culture or in "slide cell" preparations. This effect was demonstrable 5 minutes after the intravenous injection and persisted for from 6 to 12 hours after the injection. It is as marked in rabbits receiving only a single intravenous injection of endotoxin as in those previously prepared intradermally and developing a severe local Shwartzman reaction on intravenous injection. The preparation of the skin for the Shwartzman reaction does not in itself result in appreciable changes of leucocyte migration. The production of the effect depends upon some action in vivo, since leucocytes of uninjected rabbits migrate normally from the buffy coat in plasma substrates to which large concentrations of endotoxin are added in vitro. The inhibitory effect, as observed in these experiments, also depends upon the added influence of centrifugation. Leucocytes from a rabbit receiving endotoxin intravenously migrate normally from uncentrifuged lung or spleen fragments and migrate normally in blood on the warm stage prior to centrifugation. Identical centrifugation does not affect leucocytes from uninjected animals. The heparin inhibition of the local Shwartzman reaction does not alter this effect of endotoxins on leucocytes. Its possible role in the production of leucopenia and of the local Shwartzman reaction is briefly discussed.

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