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

Jianfeng Wang,Xiaodi Niu,Shui Liu,Xuming Deng,Bowen Liu

doi:10.3389/fmicb.2019.01496

Jianfeng Wang, Xiaodi Niu + Show 3 more

Open Access

https://doi.org/10.3389/fmicb.2019.01496

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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.

Highlights

Listeria monocytogenes, a rare but deadly microbe, is an intracellular pathogen that is responsible for the disease listeriosis in humans and other animal species
Consistent with the results from a previous study (Kastbjerg et al, 2010), the addition of disinfectants effectively attenuated the expression of hly (Figure 1F), while no inhibition of hly expression was observed in the presence of luteolin (Figure 1F). These results indicated that luteolin treatment had no influence on the transcription of hly and that the attenuation of listeriolysin O (LLO) production by luteolin may be due to the inhibition of hly translation
Similar to L. monocytogenes, for most bacteria, pathogenicity is largely dependent on various virulence factors, such as pore-forming toxin, sortase, and secretion systems (Lee and Kessler, 2009; Camejo et al, 2011; Bradshaw et al, 2015)

Summary

Introduction

A rare but deadly microbe, is an intracellular pathogen that is responsible for the disease listeriosis in humans and other animal species. This disease is usually caused by the ingestion of food contaminated with L. monocytogenes, which can grow well at refrigerated temperatures (4–10◦C), as well as at low pH and high salt concentrations, all of which are typically used for food preservation (Dussurget et al, 2014). Infections were reported in 28 states, and the outbreak lasted approximately 100 days During this disaster, there were a total of 146 patients with invasive disease, 30 deaths and one miscarriage. Those who died ranged in age from 48 to 96 years, with a median age of 82.5 years (McCollum et al, 2013)

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