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Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue

Department of Microbiology, The University of Chicago, 920 E. 58th Street Chicago, IL 60637, USA
Department of Pediatrics, The University of Chicago, 5721 S. Maryland Ave. Chicago, IL 60637, USA
Author to whom correspondence should be addressed.
Toxins 2013, 5(6), 1140-1166;
Received: 27 April 2013 / Revised: 28 May 2013 / Accepted: 3 June 2013 / Published: 13 June 2013
(This article belongs to the Special Issue Pore-Forming Toxins)
Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small β-barrel pore-forming toxin α-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of α-hemolysin action as nucleated cells also exhibited distinct responses to intoxication. The hemolysin, most aptly referred to as α-toxin based on its broad range of cellular specificity, has long been recognized as an important cause of injury in the context of both skin necrosis and lethal infection. The recent identification of ADAM10 as a cellular receptor for α-toxin has provided keen insight on the biology of toxin action during disease pathogenesis, demonstrating the molecular mechanisms by which the toxin causes tissue barrier disruption at host interfaces lined by epithelial or endothelial cells. This review highlights both the historical studies that laid the groundwork for nearly a century of research on α-toxin and key findings on the structural and functional biology of the toxin, in addition to discussing emerging observations that have significantly expanded our understanding of this toxin in S. aureus disease. The identification of ADAM10 as a proteinaceous receptor for the toxin not only provides a greater appreciation of truths uncovered by many historic studies, but now affords the opportunity to more extensively probe and understand the role of α-toxin in modulation of the complex interaction of S. aureus with its human host. View Full-Text
Keywords: α-toxin; Staphylococcus aureus; pore-forming toxins; ADAM10; cellular responses; S. aureus vaccine and therapeutic α-toxin; Staphylococcus aureus; pore-forming toxins; ADAM10; cellular responses; S. aureus vaccine and therapeutic
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Berube, B.J.; Wardenburg, J.B. Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue. Toxins 2013, 5, 1140-1166.

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