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Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells

Abstract : Listeria monocytogenes causes listeriosis, a foodborne disease that poses serious risks to fetuses, newborns and immunocompromised adults. This intracellular bacterial pathogen proliferates in the host cytosol and exploits the host actin polymerization machinery to spread from cell-to-cell and disseminate in the host. Here, we report that during several days of infection in human hepatocytes or trophoblast cells, L. monocytogenes switches from this active motile lifestyle to a stage of persistence in vacuoles. Upon intercellular spread, bacteria gradually stopped producing the actin-nucleating protein ActA and became trapped in lysosome-like vacuoles termed Listeria-Containing Vacuoles (LisCVs). Subpopu-lations of bacteria resisted degradation in LisCVs and entered a slow/non-replicative state. During the subculture of host cells harboring LisCVs, bacteria showed a capacity to cycle between the vacuolar and the actin-based motility stages. When ActA was absent, such as in ΔactA mutants, vacuolar bacteria parasitized host cells in the so-called " viable but non-culturable " state (VBNC), preventing their detection by conventional colony counting methods. The exposure of infected cells to high doses of gentamicin did not trigger the formation of LisCVs, but selected for vacuolar and VBNC bacteria. Together, these results reveal the ability of L. monocytogenes to enter a persistent state in a subset of epithelial cells, which may favor the asymptomatic carriage of this pathogen, lengthen the incubation period of lis-teriosis, and promote bacterial survival during antibiotic therapy. Author summary L. monocytogenes is a model intracellular pathogen that replicates in the cytoplasm of mammalian cells and disseminate in the host using actin-based motility. Here, we reveal that L. monocytogenes changes its lifestyle and persists in lysosomal vacuoles during long-PLOS Pathogens
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Mounia Kortebi, Eliane E. Milohanic, Gabriel Mitchell, Christine Péchoux, Marie-Christine Prévost, et al.. Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells. PLoS Pathogens, 2017, 13 (11), pp.e1006734. ⟨10.1371/journal.ppat.1006734⟩. ⟨pasteur-01740291⟩



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