The role of streptococcal toxins in disease

Mitchell, Tim

doi:10.1046/j.1365-2672.1998.0840s1119s.x

Journal of Applied Microbiology

1998

DOI: 10.1046/j.1365-2672.1998.0840s1119s.x

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The role of streptococcal toxins in disease

Tim Mitchell

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2001

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“…At sublethal concentrations, the related cytotoxin pneumolysin has been shown to have a range of effects on the immune system (16), including the inhibition of respiratory burst in neutrophils and stimulation of interleukin-1 and tumor necrosis factor production from human monocytes (5,21). Indeed, the effects on host cells of pneumolysin and other related cytolysins, by direct cytotoxic activity or by interference with the defense and immune cell functions, including chemotaxis and migration, respiratory burst, phagocytosis, and other modulations of the immune response, have been catalogued extensively (2).…”

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Effect on Polymorphonuclear Cell Function of a Human-Specific Cytotoxin, Intermedilysin, Expressed by Streptococcus intermedius

et al. 2001

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Streptococcus intermedius is a member of the normal flora of the mouth but is also an opportunistic pathogen associated with purulent infections at oral and nonoral sites. Intermedilysin (ILY) has been shown to be a cytolysin capable of generating pores in the cell membrane of erythrocytes demonstrable by electron microscopy. This effect has been shown to be specific for human cells. Since polymorphonuclear cells (PMNs) are the main cell involved in innate immunity we investigated the effect of purified intermedilysin from Streptococcus intermedius on PMN function. Active ILY at a concentration of 40 ng/l caused a significant decrease in the number of intact PMNs after 60 min. The active cytolysin, when compared with heat-inactivated ILY, did not appear to be chemotactic for the PMNs but did cause an increase in intracellular calcium, with increased cell surface CD11b expression, metabolic burst, and phagocytosis of Staphylococcus aureus. These findings may have implications for the role of ILY in deep-seated abscesses.The oral commensal bacterium Streptococcus intermedius is a member of the Anginosus group of streptococci (10,22) and is associated with endogenous infections leading to abscess formation in the oral cavity and at deep-seated sites, notably in the brain and other head and neck sites (1,4,7,23). Despite the clinical significance of this bacterial species, the determinants for its virulence remain unknown, and no clear correlation between a specific cell product and infection has yet been shown (20). However, recent studies have demonstrated that Streptococcus intermedius secretes a human-specific cytolysin, named intermedilysin (ILY), that directly damages host cells, including human cell lines derived from the organs associated with infections by this streptococcus (18). In the same study, purified ILY was analyzed and shown to be a 54-kDa protein in the mature form, exhibiting between 42 and 71% primary sequence homology against the cholesterol-binding cytolysin (thiol-activated cytotoxin) pneumolysin from Streptococcus pneumoniae, as determined by amino acid sequence homology to five internal ILY peptide fragments.The ily gene seems to be derived from the same ancestor as thiol-activated cytolysins and membrane pore formation (30 to 50 nm in diameter) in erythrocytes, as observed by electron microscopy (19). However, ILY showed several differences from other thiol-activated cytotoxins, notably a lack of activation by dithiothreitol, resistance to treatments with established inhibitors of this group of toxins, and a greatly reduced level of inhibition in the presence of cholesterol and anti-streptolysin O antibody (18).Subsequent determination of the distribution of the ily gene within the Anginosus species group has demonstrated that the ily gene exists only in S. intermedius and is present in all strains and that no closely related homologue to the toxin gene is distributed within the other species of the group, namely Streptococcus anginosus and Streptococcus constellatus. Furthermore, assays ...

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Effect on Polymorphonuclear Cell Function of a Human-Specific Cytotoxin, Intermedilysin, Expressed by Streptococcus intermedius

et al. 2001

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The role of streptococcal toxins in disease

Cited by 1 publication

References 31 publications

Effect on Polymorphonuclear Cell Function of a Human-Specific Cytotoxin, Intermedilysin, Expressed by Streptococcus intermedius

Effect on Polymorphonuclear Cell Function of a Human-Specific Cytotoxin, Intermedilysin, Expressed by Streptococcus intermedius

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