Structure, Function and Role in Disease of Pneumolysin, The Thiol-Activated Toxin of Streptococcus Pneumoniae
Pneumolysin, the thiol-activated toxin of Streptococcus pneumoniae is one of a family of toxins produced by four different genera of Gram positive bacteria (1). This family of toxins share a variety of physical and biological properties and exert their effects via damage to eukaryotic membranes (2). A striking feature of this family is their pronounced immunological cross-reactivity such that sera raised against one member of this family generally reacts with and often neutralizes and precipitates heterologous toxin (1). They are termed thiol-activated since they are inactivated upon oxidation and treatment with reducing agents restores full activity (1). This was thought to reflect the formation and breakage of intra-molecular disulfide bridges, a process which induces conformational changes in the protein which are reflected in their ability to interact with membranes (3). As well as mediating such changes, a single sulphydryl was postulated to be essential for activity (4). However, the role this essential cysteine plays in toxin activity is unclear. The thiol-activated toxins are thought to utilize cholesterol as receptor since their cytolytic activity is only manifest on cells which have cholesterol as part of their membranes and since free cholesterol is a potent inhibitor of cytolytic activity (1, 2). It has been postulated that this essential sulphydryl group may mediate (or is involved in) the interaction of the toxin and cholesterol (6). It should be noted that cholesterol has not been shown conclusively to act as the receptor for these toxins.
KeywordsHemolytic Activity Cytolytic Activity Pneumococcal Infection Receptor Binding Domain Single Cysteine
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