The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli

Ziyang Hao, Hubing Lou, Rongfeng Zhu, Jiuhe Zhu, Dianmu Zhang, Boxuan Simen Zhao, Shizhe Zeng, Xing Chen, Jefferson Chan, Chuan He, Peng R. Chen

Research output: Contribution to journalArticle

Abstract

The widely conserved multiple antibiotic resistance regulator (MarR) family of transcription factors modulates bacterial detoxification in response to diverse antibiotics, toxic chemicals or both. The natural inducer for Escherichia coli MarR, the prototypical transcription repressor within this family, remains unknown. Here we show that copper signaling potentiates MarR derepression in E. coli. Copper(II) oxidizes a cysteine residue (Cys80) on MarR to generate disulfide bonds between two MarR dimers, thereby inducing tetramer formation and the dissociation of MarR from its cognate promoter DNA. We further discovered that salicylate, a putative MarR inducer, and the clinically important bactericidal antibiotics norfloxacin and ampicillin all stimulate intracellular copper elevation, most likely through oxidative impairment of copper-dependent envelope proteins, including NADH dehydrogenase-2. This membrane-associated copper oxidation and liberation process derepresses MarR, causing increased bacterial antibiotic resistance. Our study reveals that this bacterial transcription regulator senses copper(II) as a natural signal to cope with stress caused by antibiotics or the environment.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalNature chemical biology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hao, Z., Lou, H., Zhu, R., Zhu, J., Zhang, D., Zhao, B. S., Zeng, S., Chen, X., Chan, J., He, C., & Chen, P. R. (2014). The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli. Nature chemical biology, 10(1), 21-28. https://doi.org/10.1038/nchembio.1380