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

Autor: Perrine Bomme, Camila Valenzuela, Magdalena Gil, Yuen-Yan Chang, Chak Hon Luk, Jost Enninga, Adeline Mallet, Léa Swistak
Přispěvatelé: Dynamique des Interactions Hôte-Pathogène - Dynamics of Host-Pathogen Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), This research was supported by fellowships from Croucher Foundation (HK) and Fondation pour la Recherche Médicale (FRM) to C.H.L. and Y.Y.C.. C.H.L. is part of the Pasteur - Paris University (PPU) International PhD Program. J.E. is supported by the ERC-CoG 'Endosubvert'. The Enninga lab is part of the LabEx IBEID and Milieu Interieure. AM and PB are supported for equipment from the French Government Programme Investissements d’Avenir France BioImaging (FBI, N° ANR-10-INSB-04-01) and are also members of the LabEx IBEID., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), European Project: 682809,EndoSubvert(2017), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Institut Pasteur [Paris]
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Bacterial Diseases
Salmonella typhimurium
Salmonella
THP-1 Cells
Host cells
Cultured tumor cells
Epithelial cells
Pathology and Laboratory Medicine
medicine.disease_cause
Epithelium
Mice
White Blood Cells
Medical Conditions
Spectrum Analysis Techniques
Animal Cells
Antibiotics
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Medicine and Health Sciences
Flow cytometry
Biology (General)
Pathogen
0303 health sciences
Antimicrobials
Effector
Drugs
3T3 Cells
Virus Latency
Bacterial Pathogens
Infectious Diseases
Medical Microbiology
Spectrophotometry
Salmonella Infections
Cell lines
Cytophotometry
Pathogens
Cellular Types
Anatomy
Biological cultures
Intracellular
Research Article
Genomic Islands
Virulence Factors
QH301-705.5
Immune Cells
Immunology
Virulence
Biology
Microbiology
03 medical and health sciences
Enterobacteriaceae
Microbial Control
Virology
Genetics
medicine
Animals
Humans
Secretion
HeLa cells
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Microbial Pathogens
Molecular Biology
030304 developmental biology
Pharmacology
Intracellular pathogens
Blood Cells
Bacteria
030306 microbiology
Intracellular parasite
Macrophages
Organisms
Biology and Life Sciences
Cell Biology
RC581-607
Cell cultures
Pathogenicity island
Research and analysis methods
Biological Tissue
Vacuoles
bacteria
Parasitology
Caco-2 Cells
Immunologic diseases. Allergy
Viral Transmission and Infection
Zdroj: PLoS Pathogens
PLoS Pathogens, 2021, 17 (4), pp.e1009550. ⟨10.1371/journal.ppat.1009550⟩
PLoS Pathogens, Public Library of Science, 2021, 17 (4), pp.e1009550. ⟨10.1371/journal.ppat.1009550⟩
PLoS Pathogens, Vol 17, Iss 4, p e1009550 (2021)
PLOS Pathogens
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1009550⟩
Popis: 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.
Author summary Salmonella Typhimurium is a clinically relevant bacterial pathogen that causes Salmonellosis. It can actively or passively invade various host cell types and reside in a Salmonella-containing vacuole (SCV) within host cells. The SCV can be remodeled into a replicative niche with the aid of Salmonella Type III Secretion System 2 (T3SS2) effectors or else, the SCV is ruptured for the access of the nutrient-rich host cytosol. Depending on the infected host cell type, S. Typhimurium undertake different lifestyles that are distinct by their subcellular localization, replication rate and metabolic rate. We present here a novel fluorescent reporter system that rapidly detects S. Typhimurium lifestyles using fluorescence microscopy and flow cytometry. We identified a dormant S. Typhimurium population within enterocyte that displays capacities in host cell persistence, dormancy exit and antibiotic tolerance. We deciphered the (p)ppGpp stringent response pathway that suppresses S. Typhimurium dormancy in enterocytes while promoting dormancy in macrophages, pinpointing a divergent physiological consequence regulated by the same set of S. Typhimurium molecular mediators. Altogether, our work demonstrated the potential of fluorescent reporters in facile bacterial characterization, and revealed a dormant S. Typhimurium population in human enterocytes that are phenotypically distinct from that observed in macrophages and fibroblasts.
Databáze: OpenAIRE
Externí odkaz: