Luteolin inhibits listeriolysin o translation by directly targeting the coding region of the hlymRNA

Abstract

Listeriolysin O (LLO) is necessary for bacterial escape from the phagosome into the cytoplasm, which suggests that targeting LLO may be an alternative strategy to combat Listeria monocytogenes-mediated infection. Here, luteolin, a natural compound without anti-bacterial activity, as indentified as effective inhibitor of LLO by translationally inhibiting the production of LLO. Additionally, luteolin-treated L. monocytogenes displayed reductions in cytoplasmic growth, cytotoxicity and phagosome escape within macrophages. Molecular modeling and mutational analysis revealed a direct interaction between luteolin and the 5' coding region (A818, U819, G820, and U830 located in nt 814-849) of the mRNA of hly, the gene encoding LLO, which interfered with its translation. Together, our data demonstrate that luteolin may be used as a novel therapeutic and lead compound for treating L. monocytogenes infection.