Studies on the binding of staphylococcal 125I-labeled α-toxin to rabbit erythrocytes

Cassidy, Paul; Harshman, Sidney

doi:10.1021/bi00656a016

Cited by 99 publications

(84 citation statements)

References 20 publications

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“…However, a high-affinity interaction of the toxin with a proteinaceous eukaryotic receptor has been suggested because rabbit erythrocytes are significantly more sensitive to Hla than human erythrocytes, correlating with the identification of 1,200-5,000 toxin-binding sites per rabbit cell (8, 9). Binding is saturable and time dependent, consistent with a ligand-receptor interaction (8,10). In addition to these data, membrane lipids seem to be central to the interaction of the toxin with the eukaryotic cell.…”

mentioning

confidence: 75%

“…Although the requirement for membrane lipids in toxin biology has been well described, a model proposing these as the sole cell-binding moiety fails to explain several important observations. Most notably, the species specificity of the toxin implies a proteinaceous receptor, because liposomes mirroring rabbit and human red blood cells do not parallel the sensitivities of these cells (10). Further, protease treatment of highly sensitive rabbit red blood cells abrogates toxin binding (10).…”

Section: Discussionmentioning

confidence: 99%

“…Most notably, the species specificity of the toxin implies a proteinaceous receptor, because liposomes mirroring rabbit and human red blood cells do not parallel the sensitivities of these cells (10). Further, protease treatment of highly sensitive rabbit red blood cells abrogates toxin binding (10). The identification of ADAM10 as an Hla-interacting protein that is required for initial toxin binding and multiple cellular cytotoxic insults provides important insight into how Hla engages the host cell.…”

Section: Discussionmentioning

confidence: 99%

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Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus α-hemolysin–mediated cellular injury

Wilke¹,

Wardenburg

2010

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

404

418

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Staphylococcus aureus α-hemolysin (Hla), a potent cytotoxin, plays an important role in the pathogenesis of staphylococcal diseases, including those caused by methicillin-resistant epidemic strains. Hla is secreted as a water-soluble monomer that undergoes a series of conformational changes to generate a heptameric, β-barrel structure in host membranes. Structural maturation of Hla depends on its interaction with a previously unknown proteinaceous receptor in the context of the cell membrane. It is reported here that a disintegrin and metalloprotease 10 (ADAM10) interacts with Hla and is required to initiate the sequence of events whereby the toxin is transformed into a cytolytic pore. Hla binding to the eukaryotic cell requires ADAM10 expression. Further, ADAM10 is required for Hlamediated cytotoxicity, most notably when the toxin is present at low concentrations. These data thus implicate ADAM10 as the probable high-affinity toxin receptor. Upon Hla binding, ADAM10 relocalizes to caveolin 1-enriched lipid rafts that serve as a platform for the clustering of signaling molecules. It is demonstrated that the Hla-ADAM10 complex initiates intracellular signaling events that culminate in the disruption of focal adhesions.pore-forming cytotoxin | cellular receptor T he Gram-positive extracellular pathogen Staphylococcus aureus is one of the leading causes of human bacterial infection. As a commensal of the skin, S. aureus is well positioned to cause infection of the skin and soft tissues, the bloodstream, and the lower respiratory tract, which are the principal sites of clinically relevant infection (1, 2). To facilitate entry and spread through the host tissue, S. aureus encodes a number of virulence factors that allow the organism to breach structural and immunological barriers to infection. One of the most prominent and well-characterized virulence factors produced by S. aureus is α-hemolysin (Hla), a pore-forming cytotoxin implicated in the pathogenesis of sepsis, pneumonia, and severe skin infection (3-6). Pore formation on susceptible host cell membranes triggers alterations in ion gradients, loss of membrane integrity, activation of stress-signaling pathways, and cell death (3, 7). Hla binds to most eukaryotic cells, often by a nonspecific adsorptive mechanism requiring micromolar concentrations of toxin (8). However, a high-affinity interaction of the toxin with a proteinaceous eukaryotic receptor has been suggested because rabbit erythrocytes are significantly more sensitive to Hla than human erythrocytes, correlating with the identification of 1,200-5,000 toxin-binding sites per rabbit cell (8, 9). Binding is saturable and time dependent, consistent with a ligand-receptor interaction (8,10). In addition to these data, membrane lipids seem to be central to the interaction of the toxin with the eukaryotic cell. Membrane cholesterol or sphingomyelin depletion abrogates toxin binding and cytotoxicity, and the addition of exogenous phosphocholine disrupts toxin binding and impairs rabbit red cell hemolysis (11)....

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mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus α-hemolysin–mediated cellular injury

Wilke¹,

Wardenburg

2010

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

404

418

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“…In fact, it has been proposed that one or more of these cell types, not RBC, may be the primary target for AT lysis in human S. aureus infections (7,15,38). Therefore, we tested the purified MAbs for the ability to prevent nAT-mediated lysis of the human cell lines A549 (alveolar epithelial cell line) and THP-1 (monocytic cell line).…”

Section: Monoclonal Antibody Generationmentioning

confidence: 99%

Identification of Anti-Alpha Toxin Monoclonal Antibodies That Reduce the Severity of Staphylococcus aureus Dermonecrosis and Exhibit a Correlation between Affinity and Potency

Tkaczyk¹,

Liu²,

Varkey³

et al. 2012

Clin. Vaccine Immunol.

112

140

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“…Despite considerable effort, the nature of the interaction of the toxin with membranes of sensitive cells is still unclear. From the results of binding studies with toxin which had lost its lytic activity by radioiodination or heating, it was concluded that the high sensitivity of rabbit erythrocytes to toxin-induced lysis was the result of the presence of high specificity toxin receptors on the membrane Harshman, 1973 and1976a;Kato et al, 1975a andBarei and Fackrell, 1979;Lo and Fackrell, 1979), but more recent data support a less specific lytic mechanism involving hydrophobic interaction of toxin with membranes resulting in transmembrane pore formation (Fussle et al, 1981). Our observations on the characteristics of binding of radioiodinated toxin with full haemolytic activity to erythrocytes are reported here.…”

Section: Introductionmentioning

confidence: 99%

Binding of 125I-Alpha Toxin of Staphylococcus Aureus to Erythrocytes

Phimister

Freer

1984

Journal of Medical Microbiology

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SUMMARY. Alpha toxin purified from Staphylococcus aureus strain Wood 46 and radioiodinated by the lactoperoxidase method retained full haemolytic activity and was used to study factors affecting binding to rabbit and horse erythrocytes. A relatively fixed percentage of added toxin bound to both cell types; the percentage bound was independent of temperature, pH, cell concentration and toxin concentration. Neither a 50-fold excess of native toxin nor Concanavalin A inhibited the binding of iodinated toxin to erythrocytes. The results suggest that differences in the sensitivity of erythrocytes to haemolysis do not reflect the abundance of high affinity toxin receptors on sensitive cells, but are more probably the result of differences in the intrinsic stability of the membrane and its sensitivity to perturbation by amphiphilic agents.

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Studies on the binding of staphylococcal 125I-labeled α-toxin to rabbit erythrocytes

Cited by 99 publications

References 20 publications

Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus α-hemolysin–mediated cellular injury

Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus α-hemolysin–mediated cellular injury

Identification of Anti-Alpha Toxin Monoclonal Antibodies That Reduce the Severity of Staphylococcus aureus Dermonecrosis and Exhibit a Correlation between Affinity and Potency

Binding of 125I-Alpha Toxin of Staphylococcus Aureus to Erythrocytes

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