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Deletion of glutaredoxin promotes oxidative tolerance and intracellular infection in Listeria monocytogenes

Sun, J., Hang, Y., Han, Y., Zhang, X., Gan, L., Cai, C., Chen, Z., Yang, Y., Song, Q., Shao, C., Yang, Y., Zhou, Y., Wang, X., Cheng, C. and Song, H. (2019) Deletion of glutaredoxin promotes oxidative tolerance and intracellular infection in Listeria monocytogenes. Virulence, 10 (1). pp. 910-924.

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Link to Published Version: https://doi.org/10.1080/21505594.2019.1685640
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Abstract

Thiol-disulfide glutaredoxin systems of bacterial cytoplasm favor reducing conditions for the correct disulfide bonding of functional proteins, and therefore were employed by bacteria to defend against oxidative stress. Listeria monocytogenes has been shown to encode a putative glutaredoxin, Grx (encoded by lmo2344), while the underlying roles remain unknown. Here we suggest an unexpected role of L. monocytogenes Grx in oxidative tolerance and intracellular infection. The recombinant Grx was able to efficiently catalyze the thiol-disulfide oxidoreduction of insulin in the presence of DTT as an election donor. Unexpectedly, the deletion of grx resulted in a remarkably increased tolerance and survival ability of this bacteria when exposed to various oxidizing agents, including diamide, and copper and cadmium ions. Furthermore, loss of grx significantly promoted bacterial invasion and proliferation in human epithelial Caco-2 cells and murine macrophages, as well as a notably increasing invasion but not cell-to-cell spread in the murine fibroblasts L929 cells. More importantly, L. monocytogenes lacking the glutaredoxin exhibited more efficient proliferation and recovery in the spleens and livers of the infected mice, and hence became more virulent by upregulating the virulence factors, InlA and InlB. In summary, we here for the first time demonstrated that L. monocytogenes glutaredoxin plays a counterintuitive role in bacterial oxidative resistance and intracellular infection, which is the first report to provide valuable evidence for the role of glutaredoxins in bacterial infection, and more importantly suggests a favorable model to illustrate the functional diversity of bacterial Grx systems during environmental adaption and host infection.

Item Type: Journal Article
Murdoch Affiliation: School of Veterinary and Life Sciences
Publisher: Taylor & Francis
Copyright: © 2019 The Author(s).
URI: http://researchrepository.murdoch.edu.au/id/eprint/52943
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