RECON-Dependent Inflammation in Hepatocytes Enhances Listeria monocytogenes Cell-to-Cell Spread

MBio
Adelle P McFarlandJoshua J Woodward

Abstract

The oxidoreductase RECON is a high-affinity cytosolic sensor of bacterium-derived cyclic dinucleotides (CDNs). CDN binding inhibits RECON's enzymatic activity and subsequently promotes inflammation. In this study, we sought to characterize the effects of RECON on the infection cycle of the intracellular bacterium Listeria monocytogenes, which secretes cyclic di-AMP (c-di-AMP) into the cytosol of infected host cells. Here, we report that during infection of RECON-deficient hepatocytes, which exhibit hyperinflammatory responses, L. monocytogenes exhibits significantly enhanced cell-to-cell spread. Enhanced bacterial spread could not be attributed to alterations in PrfA or ActA, two virulence factors critical for intracellular motility and intercellular spread. Detailed microscopic analyses revealed that in the absence of RECON, L. monocytogenes actin tail lengths were significantly longer and there was a larger number of faster-moving bacteria. Complementation experiments demonstrated that the effects of RECON on L. monocytogenes spread and actin tail lengths were linked to its enzymatic activity. RECON enzyme activity suppresses NF-κB activation and is inhibited by c-di-AMP. Consistent with these previous findings, we found that...Continue Reading

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Citations

Dec 8, 2019·Biological Chemistry·Constance PorriniSeav-Ly Tran
Mar 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Andreas LatoschaNatalia Tschowri
Nov 4, 2020·Chembiochem : a European Journal of Chemical Biology·Shivam A ZaverJoshua J Woodward
Mar 31, 2021·Critical Reviews in Food Science and Nutrition·Karolinny Cristiny de Oliveira VieiraLizziane Kretli Winkelstroter Eller
Aug 13, 2021·Frontiers in Molecular Biosciences·Martina PasquaBianca Colonna

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Methods Mentioned

BETA
reverse transcription-PCR

Software Mentioned

MetaMorph
ImageJ

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