Salmonella enters a dormant state within human epithelial cells for persistent infection.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
04 2021
Historique:
received: 17 11 2020
accepted: 08 04 2021
revised: 12 05 2021
pubmed: 1 5 2021
medline: 11 8 2021
entrez: 30 4 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33930101
doi: 10.1371/journal.ppat.1009550
pii: PPATHOGENS-D-20-02492
pmc: PMC8115778
doi:

Substances chimiques

Virulence Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1009550

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Chak Hon Luk (CH)

Dynamics of Host-Pathogen Interactions Unit and UMR3691 CNRS, Institut Pasteur, Paris, France.
Université de Paris, Sorbonne Paris Cité, Paris, France.

Camila Valenzuela (C)

Dynamics of Host-Pathogen Interactions Unit and UMR3691 CNRS, Institut Pasteur, Paris, France.

Magdalena Gil (M)

Dynamics of Host-Pathogen Interactions Unit and UMR3691 CNRS, Institut Pasteur, Paris, France.

Léa Swistak (L)

Dynamics of Host-Pathogen Interactions Unit and UMR3691 CNRS, Institut Pasteur, Paris, France.
Université de Paris, Sorbonne Paris Cité, Paris, France.

Perrine Bomme (P)

Ultrastructural Bioimaging UTechS, C2RT, Institut Pasteur, Paris, France.

Yuen-Yan Chang (YY)

Dynamics of Host-Pathogen Interactions Unit and UMR3691 CNRS, Institut Pasteur, Paris, France.

Adeline Mallet (A)

Ultrastructural Bioimaging UTechS, C2RT, Institut Pasteur, Paris, France.

Jost Enninga (J)

Dynamics of Host-Pathogen Interactions Unit and UMR3691 CNRS, Institut Pasteur, Paris, France.
Université de Paris, Sorbonne Paris Cité, Paris, France.

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