title: The Escherichia coli small protein MntS and exporter MntP optimize the intracellular concentration of manganese.
abstract: Escherichia coli does not routinely import manganese, but it will do so when iron is unavailable, so that manganese can substitute for iron as an enzyme cofactor. When intracellular manganese levels are low, the cell induces the MntH manganese importer plus MntS, a small protein of unknown function; when manganese levels are high, the cell induces the MntP manganese exporter and reduces expression of MntH and MntS. The role of MntS has not been clear. Previous work showed that forced MntS synthesis under manganese-rich conditions caused bacteriostasis. Here we find that when manganese is scarce, MntS helps manganese to activate a variety of enzymes. Its overproduction under manganese-rich conditions caused manganese to accumulate to very high levels inside the cell; simultaneously, iron levels dropped precipitously, apparently because manganese-bound Fur blocked the production of iron importers. Under these conditions, heme synthesis stopped, ultimately depleting cytochrome oxidase activity and causing the failure of aerobic metabolism. Protoporphyrin IX accumulated, indicating that the combination of excess manganese and iron deficiency had stalled ferrochelatase. The same chain of events occurred when mutants lacking MntP, the manganese exporter, were exposed to manganese. Genetic analysis suggested the possibility that MntS exerts this effect by inhibiting MntP. We discuss a model wherein during transitions between low- and high-manganese environments E. coli uses MntP to compensate for MntH overactivity, and MntS to compensate for MntP overactivity.
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Martin
authors.affiliation: Department of Chemistry, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, United States of America.
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Waters
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America.
authors.forename: Gisela
authors.initials: G
authors.lastname: Storz
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: Imlay
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism* / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; C568362:MntP protein, E coli; C568361:MntS protein, E coli; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D008345:Manganese; D007501:Iron