AUTHOR=Xu Lei , Zhou Yonglin , Xu Jingwen , Xu Xiangzhu , Lu Gejin , Lv Qianghua , Wei Lijuan , Deng Xuming , Shen Xue , Feng Haihua , Wang Jianfeng 

TITLE=Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.977051

DOI=10.3389/fimmu.2022.977051

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p><italic>Listeria monocytogenes</italic> (<italic>L. monocytogenes</italic>), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of <italic>L. monocytogenes</italic>-host interactions.</p></sec><sec><title>Methods</title><p>Hemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis. Histological analysis, ELISA assay and biochemistry detection were conducted to assess <italic>in vivo</italic> efficacy of candidates.</p></sec><sec><title>Results</title><p>In the present study, natural terpenoid atractylodin was characterized as an alternative drug candidate for the treatment of <italic>L. monocytogenes</italic> by the regulation of LLO function and host Nrf2/NLRP3 signaling pathway. Notably, <italic>in vivo</italic> infection model by <italic>L. monocytogenes</italic> also highlighted that atractylodin treatment provided effective therapeutic benefits, as evidenced by decreased bacterial burden and diminished inflammation. Congruently, the survival rate of <italic>L. monocytogenes</italic>-infection mice increased significantly from 10.0% to 40.0% by atractylodin treatment.</p></sec><sec><title>Conclusion</title><p>Collectively, our study showed for the first time that atractylodin has tremendous potential to attenuate <italic>L. monocytogenes</italic> pathogenicity by blocking LLO pore formation and mediating the suppression of inflammation and oxidative stress, providing a promising therapeutic strategy and broadening the applications of atractylodin against <italic>L. monocytogenes</italic> infection.</p></sec>