2. Academic Validation
  3. BacFlash signals acid-resistance gene expression in bacteria

BacFlash signals acid-resistance gene expression in bacteria

  • Cell Res. 2021 Jun;31(6):703-712. doi: 10.1038/s41422-020-00431-3.
Di Wu  # 1,  Wenfeng Qi  # 1,  Wei Nie  # 1 2,  Zhengyuan Lu 1,  Yongxin Ye 1,  Jinghang Li 1,  Tao Sun 1,  Yufei Zhu 1 2,  Heping Cheng 3 4,  Xianhua Wang 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
  • 2 Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing, Jiangsu, China.
  • 3 State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, 100871, China. chengp@pku.edu.cn.
  • 4 Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing, Jiangsu, China. chengp@pku.edu.cn.
  • 5 State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, 100871, China. xianhua@pku.edu.cn.
  • 6 Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing, Jiangsu, China. xianhua@pku.edu.cn.
  • # Contributed equally.
PMID: 33159153 DOI: 10.1038/s41422-020-00431-3
Abstract

Intracellular pH (pHi) homeostasis is crucial for cellular functions and signal transduction across all kingdoms of life. In particular, Bacterial pHi homeostasis is important for physiology, ecology, and pathogenesis. Here we report an exquisite Bacterial acid-resistance (AR) mechanism in which proton leak elicits a pre-emptive AR response. A single Bacterial cell undergoes quantal electrochemical excitation, termed "BacFlash", which consists of membrane depolarization, transient pHi rise, and bursting production of Reactive Oxygen Species. BacFlash ignition is dictated by acid stress in the form of proton leak across the plasma membrane and the rate of BacFlash occurrence is reversely correlated with the pHi buffering capacity. Through genome-wide screening, we further identify the ATP Synthase Fo complex subunit a as the putative proton sensor for BacFlash biogenesis. Importantly, persistent BacFlash hyperactivity activates transcription of a panel of key AR genes and predisposes the cells to survive imminent extreme acid stress. These findings demonstrate a prototypical coupling between electrochemical excitation and nucleoid gene expression in prokaryotes.

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