Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus

Brucellosis, caused by the intracellular pathogen Brucella, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal...

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Main Authors: Feijie Zhi, Kemeng Liu, Hao Geng, Mengru Su, Jian Xu, Lei Fu, Ke Ma, Pengcheng Gao, Lvfeng Yuan, YueFeng Chu
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2024.2406274
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author Feijie Zhi
Kemeng Liu
Hao Geng
Mengru Su
Jian Xu
Lei Fu
Ke Ma
Pengcheng Gao
Lvfeng Yuan
YueFeng Chu
author_facet Feijie Zhi
Kemeng Liu
Hao Geng
Mengru Su
Jian Xu
Lei Fu
Ke Ma
Pengcheng Gao
Lvfeng Yuan
YueFeng Chu
author_sort Feijie Zhi
collection DOAJ
description Brucellosis, caused by the intracellular pathogen Brucella, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in Brucella. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in B. abortus. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in B. abortus by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of arsR2 attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic Brucella species.
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language English
publishDate 2024-12-01
publisher Taylor & Francis Group
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series Emerging Microbes and Infections
spelling doaj-art-9fb962bdfd0a480ea3d05e8e6211e8862025-08-20T01:55:12ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2406274Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortusFeijie Zhi0Kemeng Liu1Hao Geng2Mengru Su3Jian Xu4Lei Fu5Ke Ma6Pengcheng Gao7Lvfeng Yuan8YueFeng Chu9State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, People’s Republic of ChinaBrucellosis, caused by the intracellular pathogen Brucella, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in Brucella. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in B. abortus. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in B. abortus by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of arsR2 attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic Brucella species.https://www.tandfonline.com/doi/10.1080/22221751.2024.2406274BrucellaArsRT4SSVjbRvirulence
spellingShingle Feijie Zhi
Kemeng Liu
Hao Geng
Mengru Su
Jian Xu
Lei Fu
Ke Ma
Pengcheng Gao
Lvfeng Yuan
YueFeng Chu
Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus
Emerging Microbes and Infections
Brucella
ArsR
T4SS
VjbR
virulence
title Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus
title_full Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus
title_fullStr Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus
title_full_unstemmed Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus
title_short Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus
title_sort copper sensing transcription factor arsr2 regulates vjbr to sustain virulence in brucella abortus
topic Brucella
ArsR
T4SS
VjbR
virulence
url https://www.tandfonline.com/doi/10.1080/22221751.2024.2406274
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