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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.

Luteolin Inhibits Listeriolysin O Translation by Directly Targeting the Coding Region of the hly mRNA