BACKGROUND Histamine is a key mediator of the anti-inflammatory activity conferred by the probiotic organism Lactobacillus reuteri ATCC PTA 6475 in animal models of colitis and colorectal cancer. In L. reuteri, histamine synthesis and secretion requires L-histidine decarboxylase and a L-histidine/histamine exchanger. Chloride channel (ClC)-family proton/chloride antiporters have been proposed to act as electrochemical shunts in conjunction with amino acid decarboxylase systems, correcting ion imbalances generated by decarboxylation through fixed ratio exchange of two chloride ions for one proton. This family is unique among transporters by facilitating ion flux in either direction. Here we examine the histidine decarboxylase system in relation to ClC antiporters in the probiotic organism Lactobacillus reuteri. RESULTS In silico analyses reveal that L. reuteri possesses two ClC transporters, EriC and EriC2, as well as a complete histidine decarboxylase gene cluster (HDC) for the synthesis and export of histamine. When the transport activity of either proton/chloride antiporter is disrupted by genetic manipulation, bacterial histamine output is reduced. Using fluorescent reporter assays, we further show that ClC transporters affect histamine output by altering intracellular pH and membrane potential. ClC transport also alters the expression and activity of two key HDC genes: the histidine decarboxylase (hdcA) and the histidine/histamine exchanger (hdcP). CONCLUSIONS Histamine production is a potentially beneficial feature for intestinal microbes by promoting long-term colonization and suppression of inflammation and host immune responses. ClC transporters may serve as tunable modulators for histamine production by L. reuteri and other gut microbes.

中文翻译：

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ClC 转运蛋白活性通过改变细胞内 pH 值和膜电位来调节罗伊氏乳杆菌中的组氨酸分解代谢。


背景组胺是益生菌罗伊氏乳杆菌 ATCC PTA 6475 在结肠炎和结直肠癌动物模型中所赋予的抗炎活性的关键介质。在罗伊氏乳杆菌中，组胺合成和分泌需要 L-组氨酸脱羧酶和 L-组氨酸/组胺交换剂。氯离子通道 (ClC) 家族质子/氯离子逆向转运蛋白被提议与氨基酸脱羧酶系统一起充当电化学分流器，通过两个氯离子与一个质子的固定比例交换来纠正脱羧产生的离子不平衡。该家族通过促进任一方向的离子通量而在转运蛋白中是独一无二的。在这里，我们研究了益生菌罗伊氏乳杆菌中与 ClC 反向转运蛋白相关的组氨酸脱羧酶系统。结果 计算机分析显示，罗伊氏乳杆菌拥有两种 ClC 转运蛋白，EriC 和 EriC2，以及用于合成和输出组胺的完整组氨酸脱羧酶基因簇 (HDC)。当质子/氯离子逆向转运蛋白的转运活性被基因操作破坏时，细菌组胺的输出就会减少。使用荧光报告分析，我们进一步表明 ClC 转运蛋白通过改变细胞内 pH 值和膜电位来影响组胺输出。 ClC 转运还会改变两个关键 HDC 基因的表达和活性：组氨酸脱羧酶 (hdcA) 和组氨酸/组胺交换器 (hdcP)。结论 组胺的产生是肠道微生物的潜在有益特征，可促进长期定植并抑制炎症和宿主免疫反应。 ClC 转运蛋白可以作为罗伊氏乳杆菌和其他肠道微生物产生组胺的可调调节剂。