期刊
PLOS PATHOGENS
卷 13, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1006734
关键词
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资金
- French National Research Agency (EPILIS) [ANR 11 BSV3 00301]
- INRA (dept. MICA grant AO Blanc)
- French Ligue Nationale Contre le Cancer (comite regional d'lle-de-France) [LNCC 131/12]
- iXcore Foundation for Research
- Lidex ALIAS of Universite Paris-Saclay
- INRA (dept.MICA)
- National Institutes of Health [1P01 AI063302, 1R01 AI027655]
- Fonds de Recherche du Quebec-Sante (FRQS)
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- INFECT-ERA (PROANTILIS)
- Labex IBEID
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). Subpopulations 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.actA 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 listeriosis, and promote bacterial survival during antibiotic therapy.
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