title: The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms.
abstract: Copper is an essential metal which is used as a cofactor in several enzymes and is required for numerous essential biochemical reactions. However, free copper ions can be toxic to cellular systems if the intracellular concentration is not tightly regulated. In this study we show that Staphylococcus aureus copper resistance is not the same in every staphylococcal isolate, but in fact varies considerably between clinical strains. Hyper-copper-resistance was shown to be due to the carriage of an additional plasmid-encoded copper homeostasis mechanism, copBmco. This plasmid can be transferred into the copper-sensitive S. aureus Newman to confer a hyper-copper-resistant phenotype, showing that copper resistance has the potential to spread to other S. aureus strains. This is the first time that plasmid-encoded copper resistance has been reported and shown to be transferable between pathogenic bacteria isolated from humans. A homologue of the Bacillus subtilis and Mycobacterium tuberculosis CsoR regulators was identified in S. aureus. The S. aureus csoR gene is conserved in all sequenced S. aureus genomes and was found to be copper-induced and transcribed along with two downstream genes: a putative copper chaperone (csoZ) and a hypothetical gene. Mutational and complementation studies showed that unlike other homologues, the S. aureus CsoR negatively regulates both chromosomal and plasmid-encoded copper homeostasis mechanisms in response to excess-copper conditions.
authors.affiliation: Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baker
authors.forename: Mrittika
authors.initials: M
authors.lastname: Sengupta
authors.forename: Radheshyan K
authors.initials: RK
authors.lastname: Jayaswal
authors.forename: Julie A
authors.initials: JA
authors.lastname: Morrissey
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002876:Chromosomes, Bacterial / Q000235:genetics; D003300:Copper / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D009876:Operon; D010957:Plasmids / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D003300:Copper