Open AccessSalmonella enters a dormant state within human epithelial cells for persistent infection
Author(s) -
Chak Hon Luk,
Camila Valenzuela,
Magdalena Gil,
Léa Swistak,
Perrine Bomme,
Yuen-Yan Chang,
Adeline Mallet,
Jost Enninga
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009550
Subject(s) - salmonella , biology , microbiology and biotechnology , virulence , intracellular , intracellular parasite , pathogenicity island , type three secretion system , secretion , effector , pathogen , vacuole , flow cytometry , shigella , bacteria , cytoplasm , genetics , gene , biochemistry
Salmonella Typhimurium ( S . Typhimurium) is an enteric bacterium capable of invading a wide range of hosts, including rodents and humans. It targets different host cell types showing different intracellular lifestyles. S . Typhimurium colonizes different intracellular niches and is able to either actively divide at various rates or remain dormant to persist. A comprehensive tool to determine these distinct S . Typhimurium lifestyles remains lacking. Here we developed a novel fluorescent reporter, Salmonella INtracellular Analyzer (SINA), compatible for fluorescence microscopy and flow cytometry in single-bacterium level quantification. This identified a S . Typhimurium subpopulation in infected epithelial cells that exhibits a unique phenotype in comparison to the previously documented vacuolar or cytosolic S . Typhimurium. This subpopulation entered a dormant state in a vesicular compartment distinct from the conventional Salmonella -containing vacuoles (SCV) as well as the previously reported niche of dormant S . Typhimurium in macrophages. The dormant S . Typhimurium inside enterocytes were viable and expressed Salmonella Pathogenicity Island 2 (SPI-2) virulence factors at later time points. We found that the formation of these dormant S . Typhimurium is not triggered by the loss of SPI-2 effector secretion but it is regulated by (p)ppGpp-mediated stringent response through RelA and SpoT. We predict that intraepithelial dormant S . Typhimurium represents an important pathogen niche and provides an alternative strategy for S . Typhimurium pathogenicity and its persistence.