@article{b6f4df1c5a3f441984d96c92e986f6df,
title = "Intracellular growth of Brucella is mediated by Dps-dependent activation of ferritinophagy",
abstract = "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.",
author = "Hop, {Huynh Tan} and Huy, {Tran Xuan Ngoc} and Lee, {Hu Jang} and Suk Kim",
note = "Funding Information: We thank the Animal and Plant Quarantine Agency in Korea for kindly providing wild‐type 544 biovar 1 strain; Dr. Wongi Min at Gyeongsang National University, the Republic of Korea for the use of qRT–PCR; Dr. Ching‐Hao Teng at National Cheng Kung University, Republic of China for critical reading of the manuscript. This project was supported by Basic Science Research Grant No. 2018R1D1R3B05048283 (SK) and Young Researcher Program Grant No. 2018R1D1A1B07048220 (HTH) through the National Research Foundation of Korea. This project was further supported by Distinguished Scholar Program Grant No. D110‐G9603 (HTH) through the National Cheng Kung University, Taiwan. B. abortus Funding Information: We thank the Animal and Plant Quarantine Agency in Korea for kindly providing wild-type B. abortus 544 biovar 1 strain; Dr. Wongi Min at Gyeongsang National University, the Republic of Korea for the use of qRT–PCR; Dr. Ching-Hao Teng at National Cheng Kung University, Republic of China for critical reading of the manuscript. This project was supported by Basic Science Research Grant No. 2018R1D1R3B05048283 (SK) and Young Researcher Program Grant No. 2018R1D1A1B07048220 (HTH) through the National Research Foundation of Korea. This project was further supported by Distinguished Scholar Program Grant No. D110-G9603 (HTH) through the National Cheng Kung University, Taiwan. Huynh Tan Hop: Conceptualization; data curation; formal analysis; funding acquisition; investigation; methodology; writing – original draft. Tran Xuan Ngoc Huy: Formal analysis; validation; investigation; methodology; writing – review and editing. Hu Jang Lee: Conceptualization; formal analysis; validation; investigation; writing – review and editing. Suk Kim: Conceptualization; supervision; funding acquisition; investigation; writing – review and editing. The authors declare that they have no conflict of interest. Publisher Copyright: {\textcopyright} 2023 The Authors.",
year = "2023",
month = sep,
day = "6",
doi = "10.15252/embr.202255376",
language = "English",
volume = "24",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "9",
}