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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11 December 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41422-023-00900-5
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Acknowledgements
We thank Dr. Yi-Ping Wang for the gifts of pMP190 plasmid and PKUW13 and PKUW151 strains, Dr. Liangyi Chen for the gift of pHluorin plasmid, Dr. Chuanyun Li and Dr. Wanqiu Ding for bioinformatics analysis, Mr. Dapeng Zhang for helping with automated BacFlash detection, Dr. Zhenzhen Rao for ANOVA analysis, Dr. Peng Yu and Mrs. Zhengling Yang for technical assistance, and Drs. Conghui You, Shiqiang Wang, and Peng Zou for valuable comments. This work was supported by the National Key Basic Research Program of China (2017YFA0504000 and 2016YFA0500403) and the National Science Foundation of China (31670039, 81827809, 31821091 and 31971158).
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D.W., W.Q., W.N., Z.L., and Y.Z. performed experiments. Y.Y., J.L., and T.S. developed algorithms and software for automated BacFlash detection. X.W. and H.C. conceived and supervised the project and wrote the manuscript with inputs from all co-authors.
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The original online version of this article was revised: in the 'Acknowledgements' section of this article, one of the grant numbers relating to the National Science Foundation of China was incorrectly given as 8182780030 and should have been 81827809.
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Wu, D., Qi, W., Nie, W. et al. BacFlash signals acid-resistance gene expression in bacteria. Cell Res 31, 703–712 (2021). https://doi.org/10.1038/s41422-020-00431-3
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DOI: https://doi.org/10.1038/s41422-020-00431-3
