Intermedilysin

Nagamune, Hideaki; Ohnishi, C.; Katsuura, A; Taoka, Y.; Fushitani, Kenzo; Whiley, Robert A.; Yamashita, K.; Tsuji, Akihiko; Matsuda, Yoshiko; Maeda, Takuya; Korai, H.; Kitamura, S.

doi:10.1007/978-1-4899-1825-3_182

Cited by 16 publications

(18 citation statements)

References 2 publications

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“…The CDC ILY from Streptococcus intermedius posed a special problem to the dogma that cholesterol was the CDC receptor since ILY is specific for human erythrocytes (54,55). The human cell specificity of ILY was difficult to reconcile with the notion that cholesterol served as the common receptor for the CDCs.…”

Section: Figmentioning

confidence: 99%

“…Intermedilysin. ILY is expressed by Streptococcus intermedius, and as described above, it exhibits the unique characteristic of being specific for human cells (54,55) based on the ability to specifically bind to human CD59 (20). No other CDC appears to bind to a nonsterol receptor, although it is probably too early to dismiss the possibility that other CDCs might use specific receptors other than cholesterol.…”

Section: Cdc Structural Diversity and Pathogenesismentioning

confidence: 99%

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Cholesterol-Dependent Cytolysins, a Family of Versatile Pore-Forming Toxins

2005

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The cholesterol-dependent cytolysins (CDCs) are a large family of pore-forming toxins that are produced by more than 20 species from the genera Clostridium, Streptococcus, Listeria, Bacillus, and Arcanobacterium. The pore-forming mechanism of these toxins exhibits two hallmark characteristics: an absolute dependence on the presence of membrane cholesterol and the formation of an extraordinarily large pore. Each CDC is produced as a soluble monomeric protein that, with the exception of one member, is secreted by a type II secretion system. Upon encountering a eukaryotic cell, the CDCs undergo a transformation from a soluble monomeric protein to a membrane-embedded supramolecular pore complex. The conversion of the monomers to an oligomeric, membrane-inserted pore complex requires some extraordinary changes in the structure of the monomer, yet the mechanism of pore formation may be only the beginning of the CDC story.Although the CDCs are well known as beta-hemolytic proteins, it has become increasingly apparent that bacterial pathogens use these proteins in much more sophisticated ways than as simple hemolysins or general cell-lytic agents. The CDC structure also exhibits a plasticity that has allowed the evolution of unique features for some CDCs, without compromising the fundamental pore-forming mechanism. Some of these features are reflected in CDCs that activate complement, that utilize a nonsterol receptor, that exhibit a pH-sensitive, poreforming mechanism, or that can function as a protein translocation channel. As will be apparent in this review, our knowledge of how the CDCs are used by pathogens lags behind our understanding of the CDC pore-forming mechanism, although some studies have provided some provocative glimpses into how the bacterial cells use CDCs during an infection. This review will focus on the advancements in our understanding of the CDC pore-forming mechanism, the unique structural and mechanistic features that are exhibited by many of the CDCs, and how these features might contribute to pathogenesis.

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Section: Figmentioning

confidence: 99%

Section: Cdc Structural Diversity and Pathogenesismentioning

confidence: 99%

Cholesterol-Dependent Cytolysins, a Family of Versatile Pore-Forming Toxins

2005

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“…The CDC from Streptococcus intermedius, intermedilysin (ILY), exhibits an exquisite specificity for human cells (16), suggesting that cholesterol cannot be responsible for membrane recognition by ILY, yet its mechanism still seems sensitive to cholesterol (16). Also, Jacobs et al (17) have shown that the addition of exogenous cholesterol inhibited the activity of the CDC listeriolysin O (LLO) but did not prevent its binding to the membrane.…”

mentioning

confidence: 99%

Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins

Giddings

Johnson

Tweten

2003

Proc. Natl. Acad. Sci. U.S.A.

176

190

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The cholesterol-dependent cytolysins (CDCs) constitute a large family of pore-forming toxins that function exclusively on cholesterol-containing membranes. A detailed analysis of the various stages in the cytolytic mechanism of three members of the CDC family revealed that significant depletion of cholesterol from the erythrocyte membrane stalls these toxins in the prepore complex. Therefore, the depletion of membrane cholesterol prevents the insertion of the transmembrane ␤-barrel and pore formation. These unprecedented findings provide a paradigm for the involvement of cholesterol in the CDC cytolytic mechanism and that of other pore-forming toxins whose activity is enhanced by the presence of membrane cholesterol.

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“…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).…”

mentioning

confidence: 74%

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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Intermedilysin

Cited by 16 publications

References 2 publications

Cholesterol-Dependent Cytolysins, a Family of Versatile Pore-Forming Toxins

Cholesterol-Dependent Cytolysins, a Family of Versatile Pore-Forming Toxins

Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins

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

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