Intracellular growth of Brucella is mediated by Dps-dependent activation of ferritinophagy

被引:2
|
作者
Hop, Huynh Tan [1 ]
Huy, Tran Xuan Ngoc [2 ]
Lee, Hu Jang [2 ]
Kim, Suk [2 ]
机构
[1] Natl Cheng Kung Univ, Univ Ctr Biosci & Biotechnol, Tainan, Taiwan
[2] Gyeongsang Natl Univ, Coll Vet Med, Jinju, South Korea
基金
新加坡国家研究基金会;
关键词
Brucella; ferritin-like protein Dps; ferritinophagy; iron homeostasis; macrophage; DNA-BINDING PROTEIN; STRESS RESISTANCE; IRON; CELLS; ACQUISITION; INFECTION; INCREASE; ABORTUS; EVADES; SYSTEM;
D O I
10.15252/embr.202255376
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:15
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