Intracellular pH (pH_i) homeostasis is crucial for cellular functions and signal transduction across all kingdoms of life. In particular, bacterial pH_i 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 pH_i 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 pH_i buffering capacity. Through genome-wide screening, we further identify the ATP synthase F_o 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.

细胞内 pH (pH _i ) 稳态对于所有生命王国的细胞功能和信号转导至关重要。特别是，细菌 pH _i稳态对于生理学、生态学和发病机制很重要。在这里，我们报告了一种精致的细菌抗酸 (AR) 机制，其中质子泄漏引发了先发制人的 AR 反应。单个细菌细胞经历称为“BacFlash”的量子电化学激发，其包括膜去极化、瞬时 pH _i升高和活性氧物质的爆发产生。BacFlash 点火是由质子泄漏形式的酸应力决定的，BacFlash 的发生率与 pH 值_{i呈负相关。}缓冲能力。通过全基因组筛选，我们进一步确定了 ATP 合酶 F _o复合亚基 a 作为 BacFlash 生物发生的推定质子传感器。重要的是，持续的 BacFlash 过度活跃会激活一组关键 AR 基因的转录，并使细胞易于在即将到来的极端酸胁迫下生存。这些发现证明了原核生物中电化学激发和类核基因表达之间的典型耦合。