Molecular mechanism and functional significance of acid generation in the Drosophila midgut.
Molecular mechanism and functional significance of acid generation in the Drosophila midgut.
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DOI：
10.1038/srep27242
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发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Dow JA
中科院分区：
文献类型：
--
作者：
Overend G;Luo Y;Henderson L;Douglas AE;Davies SA;Dow JA
黑腹果蝇（Drosophila melanogaster）的肠道包括近端酸性区域（~pH 2），然而基因组缺乏哺乳动物胃壁细胞的H+/K+ ATP酶特征，并且对酸产生的分子机制知之甚少。在这里，我们表明，酸性区域的低pH值的维持依赖于H+ V-ATP酶，以及碳酸酐酶和五个进一步的转运蛋白或介导K+，Cl−和HCO 3 −转运的通道。在标准实验室条件下，废除低pH值不影响幼虫的存活，但对高Na+或K+负荷的昆虫是有害的。在酸性区域中pH升高的昆虫显示出对假单胞菌属病原体的易感性增加，并且肠道微生物群的关键成员（醋杆菌属和乳杆菌属）的丰度增加，这表明酸性区域具有抑菌或杀菌活性。相反，在无菌果蝇中酸性区域的pH值显著降低，表明肠道细菌在塑造肠道pH值条件中的作用。这些结果表明，酸性肠道区域保护昆虫和肠道微生物组免受病理性破坏，并阐明了在不存在H+，K+ ATP酶的情况下可以维持低pH的机制。
The gut of Drosophila melanogaster includes a proximal acidic region (~pH 2), however the genome lacks the H+/K+ ATPase characteristic of the mammalian gastric parietal cell, and the molecular mechanisms of acid generation are poorly understood. Here, we show that maintenance of the low pH of the acidic region is dependent on H+ V-ATPase, together with carbonic anhydrase and five further transporters or channels that mediate K+, Cl− and HCO3− transport. Abrogation of the low pH did not influence larval survival under standard laboratory conditions, but was deleterious for insects subjected to high Na+ or K+ load. Insects with elevated pH in the acidic region displayed increased susceptibility to Pseudomonas pathogens and increased abundance of key members of the gut microbiota (Acetobacter and Lactobacillus), suggesting that the acidic region has bacteriostatic or bacteriocidal activity. Conversely, the pH of the acidic region was significantly reduced in germ-free Drosophila, indicative of a role of the gut bacteria in shaping the pH conditions of the gut. These results demonstrate that the acidic gut region protects the insect and gut microbiome from pathological disruption, and shed light on the mechanisms by which low pH can be maintained in the absence of H+, K+ ATPase.