title: ArsP: a methylarsenite efflux permease.
abstract: Trivalent organoarsenic compounds are far more toxic than either pentavalent organoarsenicals or inorganic arsenite. Many microbes methylate inorganic arsenite (As(III)) to more toxic and carcinogenic methylarsenite (MAs(III)). Additionally, monosodium methylarsenate (MSMA or MAs(V)) has been used widely as an herbicide and is reduced by microbial communities to MAs(III). Roxarsone (3-nitro-4-hydroxybenzenearsonic acid) is a pentavalent aromatic arsenical that is used as antimicrobial growth promoter for poultry and swine, and its active form is the trivalent species Rox(III). A bacterial permease, ArsP, from Campylobacter jejuni, was recently shown to confer resistance to roxarsone. In this study, C. jejuni arsP was expressed in Escherichia coli and shown to confer resistance to MAs(III) and Rox(III) but not to inorganic As(III) or pentavalent organoarsenicals. Cells of E. coli expressing arsP did not accumulate trivalent organoarsenicals. Everted membrane vesicles from those cells accumulated MAs(III) > Rox(III) with energy supplied by NADH oxidation, reflecting efflux from cells. The vesicles did not transport As(III), MAs(V) or pentavalent roxarsone. Mutation or modification of the two conserved cysteine residues resulted in loss of transport activity, suggesting that they play a role in ArsP function. Thus, ArsP is the first identified efflux system specific for trivalent organoarsenicals.
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Madegowda
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Hiranmoy
authors.initials: H
authors.lastname: Bhattacharjee
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Barry P
authors.initials: BP
authors.lastname: Rosen
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001149:Arsenates / Q000378:metabolism; D001152:Arsenicals / Q000378:metabolism / Q000494:pharmacology; D018053:Arsenites / Q000378:metabolism* / Q000494:pharmacology; D016123:Campylobacter jejuni / Q000201:enzymology* / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000378:metabolism; D012406:Roxarsone / Q000737:chemistry / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001149:Arsenates; D001152:Arsenicals; D018053:Arsenites; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins; D013439:Sulfhydryl Reagents; D012406:Roxarsone