Public Library of Science, PLoS Pathogens, 4(17), p. e1009550, 2021
DOI: 10.1371/journal.ppat.1009550
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SalmonellaTyphimurium (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 distinctS. Typhimurium lifestyles remains lacking. Here we developed a novel fluorescent reporter,SalmonellaINtracellular Analyzer (SINA), compatible for fluorescence microscopy and flow cytometry in single-bacterium level quantification. This identified aS. Typhimurium subpopulation in infected epithelial cells that exhibits a unique phenotype in comparison to the previously documented vacuolar or cytosolicS. Typhimurium. This subpopulation entered a dormant state in a vesicular compartment distinct from the conventionalSalmonella-containing vacuoles (SCV) as well as the previously reported niche of dormantS. Typhimurium in macrophages. The dormantS. Typhimurium inside enterocytes were viable and expressedSalmonellaPathogenicity Island 2 (SPI-2) virulence factors at later time points. We found that the formation of these dormantS. 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 dormantS. Typhimurium represents an important pathogen niche and provides an alternative strategy forS. Typhimurium pathogenicity and its persistence.