Intracellular growth of Brucella is mediated by Dps-dependent activation of ferritinophagy.
Brucella
ferritin-like protein Dps
ferritinophagy
iron homeostasis
macrophage
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 09 2023
06 09 2023
Historique:
revised:
07
07
2023
received:
09
05
2022
accepted:
14
07
2023
pmc-release:
28
07
2024
medline:
7
9
2023
pubmed:
28
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
Bacteria of the genus Brucella cause brucellosis, one of the world's most common zoonotic diseases. A major contributor to Brucella's virulence is the ability to circumvent host immune defense mechanisms. Here, we find that the DNA-binding protein Dps from Brucella is secreted within the macrophage cytosol, modulating host iron homeostasis and mediating intracellular growth of Brucella. In addition to dampening iron-dependent production of reactive oxygen species (ROS), a key immune effector required for immediate bacterial clearance, cytosolic Dps mediates ferritinophagy activation to elevate intracellular free-iron levels, thereby promoting Brucella growth and inducing host cell necrosis. Inactivation of the ferritinophagy pathway by Ncoa4 gene knockout significantly inhibits intracellular growth of Brucella and host cell death. Our study uncovers an unconventional role of bacterial Dps, identifying a crucial virulence mechanism used by Brucella to adapt to the harsh environment inside macrophages.
Identifiants
pubmed: 37503678
doi: 10.15252/embr.202255376
pmc: PMC10481649
doi:
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55376Informations de copyright
© 2023 The Authors.
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