Systems-level exploitation of OxyR regulon unravels a potential antibacterial target in Pseudomonas aeruginosa
Bacteria coordinate the response to oxidative stress through LysR-type transcriptional regulator (LTTR) OxyR. However, only fragmentary information on the regulation and function of OxyR has been gleaned in the opportunistic pathogen Pseudomonas aeruginosa. Here, we delineate the OxyR regulon using multi-omics analyses. OxyR is found to positively regulate several genes involved in quorum sensing (QS) and energy metabolism. OxyR is further involved in the negative regulation of amino acid transporters that was confirmed by metabolomics analysis. Finally, we uncover gltS, an OxyR regulon gene, could be used as a potential drug potentiation target. Altogether, our results confirm that, apart from its dominant role in defense against oxidative stress in P. aeruginosa, OxyR acts as a global regulator of QS, energy metabolism and amino acid homeostasis, but also serves as a model system to identify potential antibacterial target such as gltS.
Authors
- Zheng Qing Fu (ORCID: https://orcid.org/0000-0003-1519-6192)
- Dao Wang (ORCID: https://orcid.org/0000-0001-8426-1467)
- Ruiling Sun
- Yong Chiang Tan (ORCID: https://orcid.org/0000-0002-6481-8990)
- Kaiyu Cui (ORCID: https://orcid.org/0000-0002-2205-2579)
- Ping Wang (ORCID: https://orcid.org/0000-0001-9632-4314)
- Qiuyun You (ORCID: https://orcid.org/0009-0005-8319-6831)
- Xuan Sun (ORCID: https://orcid.org/0000-0001-5670-8313)
- Qing Wei (ORCID: https://orcid.org/0000-0002-6956-6294)
- Yuwen Xia
- W YANG
- Fei Wang (ORCID: https://orcid.org/0000-0001-9459-9461)
Institutions
- University of Shanghai for Science and Technology (CN)
- Cisco Systems (China) (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Hubei University of Chinese Medicine (CN)
- Wuhan City Chinese Medicine Hospital (CN)
- Wuhan Puai Hospital (CN)
- Kementerian Kesehatan Republik Indonesia (ID)
- China Academy of Chinese Medical Sciences (CN)
- Precision Research (United States) (US)
- First Affiliated Hospital of Zhengzhou University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1038/s42003-025-08770-w
- Citations
- 1
- Primary Topic
- Bacterial biofilms and quorum sensing
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Health Commission of Hubei Province
- China Academy of Chinese Medical Sciences