title: Distinct functional roles of homologous Cu+ efflux ATPases in Pseudomonas aeruginosa.
abstract: In bacteria, most Cu(+) -ATPases confer tolerance to Cu by driving cytoplasmic metal efflux. However, many bacterial genomes contain several genes coding for these enzymes suggesting alternative roles. Pseudomonas aeruginosa has two structurally similar Cu(+) -ATPases, CopA1 and CopA2. Both proteins are essential for virulence. Expressed in response to high Cu, CopA1 maintains the cellular Cu quota and provides tolerance to this metal. CopA2 belongs to a subgroup of ATPases that are expressed in association with cytochrome oxidase subunits. Mutation of copA2 has no effect on Cu toxicity nor intracellular Cu levels; but it leads to higher H(2) O(2) sensitivity and reduced cytochrome oxidase activity. Mutation of both genes does not exacerbate the phenotypes produced by single-gene mutations. CopA1 does not complement the copA2 mutant strain and vice versa, even when promoter regions are exchanged. CopA1 but not CopA2 complements an Escherichia coli strain lacking the endogenous CopA. Nevertheless, transport assays show that both enzymes catalyse cytoplasmic Cu(+) efflux into the periplasm, albeit CopA2 at a significantly lower rate. We hypothesize that their distinct cellular functions could be based on the intrinsic differences in transport kinetic or the likely requirement of periplasmic partner Cu-chaperone proteins specific for each Cu(+) -ATPase.
authors.affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: González-Guerrero
authors.forename: Daniel
authors.initials: D
authors.lastname: Raimunda
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: José M
authors.initials: JM
authors.lastname: Argüello
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D006801:Humans; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases