1887

Abstract

Listeriolysin O (LLO), a member of the cholesterol-dependent cytolysin (CDC) family, is a major virulence factor of and contributes to bacterial escape from intracellular killing of macrophages. LLO is activated under weakly acidic conditions; however, the molecular mechanism of this pH-dependent expression of cytolytic activity of LLO is poorly understood. In this study, CDCs including LLO, ivanolysin O (ILO), seeligeriolysin O (LSO), pneumolysin (PLY), streptolysin O (SLO) and perfringolysin O (PFO) were prepared as recombinant proteins and examined for their functional changes after treatment under various pH conditions. Haemolytic and membrane cholesterol-binding activities were not affected in PLY, SLO and PFO at any pH examined. By contrast, all the -derived cytolysins, LLO, ILO and LSO, were active only at an acidic pH and rapidly inactivated under neutral or alkaline conditions. Once inactivated, LLO could not be reactivated even by a downward pH shift. The hydrophobicity of LLO treated at neutral or alkaline pH was increased. These data suggested that the pH-dependent loss of cytolytic activity appeared to be due to irreversible structural changes of domain 4 that resulted in the loss of target membrane cholesterol binding.

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2007-07-01
2020-08-14
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