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pH dependence of listeriolysin O aggregation and pore-forming ability

Lookup NU author(s): Professor Jeremy Lakey

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Abstract

Listeriolysin O (LLO) is the major factor implicated in the escape of Listeria monocytogenes from the phagolysosome. It is the only representative of cholesterol-dependent cytolysins that exhibits pH-dependent activity. Despite intense studies of LLO pH-dependence, this feature of the toxin still remains incompletely explained. Here we used fluorescence and CD spectroscopy to show that the structure of LLO is not detectably affected by pH at room temperature. We observed slightly altered haemolytic and permeabilizing activities at different pH values, which we relate to reduced binding of LLO to the lipid membranes. However, alkaline pH and elevated temperatures caused rapid denaturation of LLO. Aggregates of the toxin were able to bind Congo red and Thioflavin T dyes and were visible under transmission electron microscopy as large, amorphous, micrometer-sized assemblies. The aggregates had the biophysical properties of amyloid. Analytical ultracentrifugation indicated dimerization of the protein in acidic conditions, which protects the protein against premature denaturation in the phagolysosome, where toxin activity takes place. We therefore suggest that LLO spontaneously aggregates at the neutral pH found in the host cell cytosol and that this is a major mechanism of LLO inactivation.


Publication metadata

Author(s): Bavdek A, Kostanjsek R, Antonini V, Lakey JH, Serra MD, Gilbert RJC, Anderluh G

Publication type: Article

Publication status: Published

Journal: FEBS Journal

Year: 2012

Volume: 279

Issue: 1

Pages: 126-141

Print publication date: 25/11/2011

ISSN (print): 1742-464X

ISSN (electronic): 1742-4658

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1742-4658.2011.08405.x

DOI: 10.1111/j.1742-4658.2011.08405.x


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