Salmonella and E. coli synthesize, import, and export cadaverine, putrescine, and spermidine to maintain physiological levels and provide pH homeostasis. Both low and high intracellular levels of polyamines confer pleiotropic phenotypes or lethality. Here, we demonstrate that the previously uncharacterized inner membrane protein PaeA (YtfL) is required for reducing cytoplasmic cadaverine and putrescine concentrations. We identified paeA as a gene involved in stationary phase survival when cells were initially grown in acidic medium, in which they produce cadaverine. The paeA mutant is also sensitive to putrescine, but not to spermidine or spermine. Sensitivity to external cadaverine in stationary phase is only observed at pH > 8, suggesting that the polyamines need to be deprotonated to passively diffuse into the cell cytoplasm. In the absence of PaeA, intracellular polyamine levels increase and the cells lose viability. Degradation or modification of the polyamines is not relevant. Ectopic expression of the known cadaverine exporter, CadB, in stationary phase partially suppresses the paeA phenotype, and overexpression of PaeA in exponential phase partially complements a cadB mutant grown in acidic medium. These data support the hypothesis that PaeA is a cadaverine/putrescine exporter, reducing potentially toxic levels under certain stress conditions.

中文翻译：

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PaeA (YtfL) 防止鼠伤寒沙门氏菌和大肠杆菌中的尸胺和腐胺应激

沙门氏菌和大肠杆菌合成、输入和输出尸胺、腐胺和亚精胺，以维持生理水平并提供 pH 值稳态。多胺的低细胞内水平和高细胞内水平都赋予多效性表型或致死率。在这里，我们证明以前未表征的内膜蛋白 PaeA (YtfL) 是降低细胞质尸胺和腐胺浓度所必需的。当细胞最初在酸性培养基中生长时，我们将paeA鉴定为参与稳定期存活的基因，在酸性培养基中它们会产生尸胺。该PAEA突变体也对腐胺敏感，但对亚精胺或精胺不敏感。仅在 pH > 8 时才观察到固定相中对外部尸胺的敏感性，这表明多胺需要去质子化才能被动扩散到细胞质中。在没有 PaeA 的情况下，细胞内多胺水平增加，细胞失去活力。多胺的降解或改性无关紧要。已知尸胺输出蛋白 CadB 在固定期的异位表达部分抑制了paeA表型，而 PaeA 在指数期的过度表达部分补充了在酸性培养基中生长的cadB突变体。这些数据支持 PaeA 是尸胺/腐胺输出者的假设，在某些压力条件下降低了潜在的毒性水平。