Listeriolysin O Binding Affects Cholesterol and Phospholipid Acyl Chain Dynamics in Fluid Cholesterol‐Rich Bilayers. Issue 53 (28th August 2018)

• Record Type: Journal Article
• Authors: Kozorog, Mirijam; Sani, Marc‐Antoine; Separovic, Frances; Anderluh, Gregor
• Is Part Of: Chemistry. Volume 24:Issue 53(2018)
• Page Start: 14220
• Page End: 14225
• Publication Date: 2018-08-28
• Subjects: cholesterol-dependent cytolysins -- lipid membranes -- listeriolysin O -- pore-forming toxins -- solid-state NMR; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201802575
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Listeriolysin O (LLO) is a pore‐forming toxin that enables survival and cell‐to‐cell spread of foodborne bacterial pathogen Listeria monocytogenes, which is responsible for the life‐threatening disease, listeriosis. LLO–membrane interactions are crucial for pathogenicity of Listeria, but remained unexplained in detail at the molecular level. Here we addressed them by means of 2 H, 31 P, 13 C and 19 F solid‐state NMR spectroscopy. Different fluid and ordered cholesterol‐rich membrane lipid bilayer systems were prepared and checked for the integrity and properties in the presence of LLO. LLO has significantly changed dynamics of phospholipid acyl chains of more fluid cholesterol‐rich bilayers, whereas the lipid bilayer organization was not affected. LLO has also affected cholesterol dynamics by increasing the intensity of low frequency motions, indicating direct interactions of LLO with cholesterol. Additionally, the LLO protein was shown to interact differently with lipid membranes, depending on the properties of cholesterol‐rich membranes. The presented results, therefore, provide new insights into the interactions of the bacterial toxin LLO with cholesterol‐rich membrane systems. Abstract : Listeriolysin O is a cholesterol‐dependent cytolysin, responsible for the escape of pathogenic bacteria, Listeria monocytogenes, from the acidic phagolysosome. Listeriolysin O binds cholesterol‐rich membranes, oligomerizes, and forms pores by inserting parts of its polypeptide chain into the membrane. Solid‐state NMR experiments showed that listeriolysin O preferentially binds and perturbs the hydrophobic core of more fluid cholesterol‐rich membranes.