AUTHOR=Zhang Yu , Guo Qian , Fang Xiaowei , Yuan Mei , Hu Wenjie , Liang Xiongyan , Liu Jing , Yang Yuying , Fang Chun 

TITLE=Destroying glutathione peroxidase improves the oxidative stress resistance and pathogenicity of Listeria monocytogenes

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1122623

DOI=10.3389/fmicb.2023.1122623

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>Glutathione peroxidase is abundant in eukaryotes as an important antioxidant enzyme. However, prokaryotic glutathione peroxidase has not been thoroughly studied. <italic>Listeria monocytogenes</italic> is a facultative intracellular pathogen that is capable of causing listeriosis in animals as well as humans. Despite the fact that <italic>L. monocytogenes</italic> encodes a putative glutathione peroxidase, GSH-Px (encoded by <italic>lmo0983</italic>)), the functions of the enzyme are still unknown. Here we revealed the unusual roles of <italic>L. monocytogenes</italic> GSH-Px in bacterial antioxidants and pathogenicity.</p></sec><sec><title>Methods</title><p><italic>L. monocytogenes</italic> Lm850658 was taken as the parental strain to construct the gsh-px deletion strain and related complement strain. The effect of the gsh-px gene on the resistance of <italic>L. monocytogenes</italic> to oxidative stress was determined by measuring the concentrations of glutathione and assaying the stress survival rates under different oxidative conditions. In addition, the pathogenicity of <italic>L. monocytogenes</italic> was determined by cellular adhesion and invasion assays and mice virulence tests, and the expression of virulence factors was determined by Western blot.</p></sec><sec><title>Results</title><p>Deficiency of GSH-Px not only increased glutathione concentrations in L. monocytogenes but also enhanced its resistance to oxidative stress when exposed to copper and iron ions. In addition, the absence of gsh-px significantly improved the adhesion and invasion efficiency of <italic>L. monocytogenes</italic> to Caco-2 cells. More importantly, <italic>L. monocytogenes</italic> lacking GSH-Px could colonize and proliferate more efficiently in mice livers and spleens, enhancing the pathogenicity of L. monocytogenes by increasing the expression of virulence factors like InlA, InlB, and LLO.</p></sec><sec><title>Discussion</title><p>Taken together, we confirmed that GSH-Px of <italic>L. monocytogenes</italic> has a counter-intuitive effect on the antioxidant capacity and pathogenicity.</p></sec>