title: Molecular mechanism and functional significance of acid generation in the Drosophila midgut.
abstract: 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.
authors.affiliation: Institute of Molecular, Cell &Systems Biology, College of Medical, Veterinary &Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Gayle
authors.initials: G
authors.lastname: Overend
authors.affiliation: Department of Entomology and Department of Molecular Biology and Genetics, Cornell University, New York State, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Molecular, Cell &Systems Biology, College of Medical, Veterinary &Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Henderson
authors.affiliation: Department of Entomology and Department of Molecular Biology and Genetics, Cornell University, New York State, USA.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Douglas
authors.affiliation: Institute of Molecular, Cell &Systems Biology, College of Medical, Veterinary &Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Shireen A
authors.initials: SA
authors.lastname: Davies
authors.affiliation: Institute of Molecular, Cell &Systems Biology, College of Medical, Veterinary &Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Julian A T
authors.initials: JA
authors.lastname: Dow
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001693:Biological Transport, Active; D002256:Carbonic Anhydrases / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D012964:Sodium; D025262:Vacuolar Proton-Translocating ATPases; D002256:Carbonic Anhydrases; D011188:Potassium