title: Microcin J25 has dual and independent mechanisms of action in Escherichia coli: RNA polymerase inhibition and increased superoxide production.
abstract: Microcin J25 (MccJ25) uptake by Escherichia coli requires the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbD, ExbB, and SbmA. MccJ25 appears to have two intracellular targets: (i) RNA polymerase (RNAP), which has been described in E. coli and Salmonella enterica serovars, and (ii) the respiratory chain, reported only in S. enterica serovars. In the current study, it is shown that the observed difference between the actions of microcin on the respiratory chain in E. coli and S. enterica is due to the relatively low microcin uptake via the chromosomally encoded FhuA. Higher expression by a plasmid-encoded FhuA allowed greater uptake of MccJ25 by E. coli strains and the consequent inhibition of oxygen consumption. The two mechanisms, inhibition of RNAP and oxygen consumption, are independent of each other. Further analysis revealed for the first time that MccJ25 stimulates the production of reactive oxygen species (O(2)(*-)) in bacterial cells, which could be the main reason for the damage produced on the membrane respiratory chain.
authors.affiliation: Departamento de Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas, 4000-Tucumán, Argentina.
authors.forename: Augusto
authors.initials: A
authors.lastname: Bellomio
authors.forename: Paula A
authors.initials: PA
authors.lastname: Vincent
authors.forename: Beatriz F
authors.initials: BF
authors.lastname: de Arcuri
authors.forename: Ricardo N
authors.initials: RN
authors.lastname: Farías
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Morero
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000493:pharmacokinetics / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001430:Bacteriocins; D029968:Escherichia coli Proteins; C050900:FhuA protein, E coli; D017382:Reactive Oxygen Species; D013481:Superoxides; C020411:microcin; D002374:Catalase; C051253:katG protein, E coli; D012321:DNA-Directed RNA Polymerases