Unknown,Transcriptomics,Genomics,Proteomics

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A new structural paradigm in copper resistance in a human pathogen

ABSTRACT: Copper is essential for both innate and adaptive immune function and copper resistance has emerged as an important determinant of virulence of microbial pathogens. In the human pathogen Streptococcus pneumoniae (Spn), cytoplasmic copper resistance is mediated by an operon encoding the copper-responsive repressor CopY, CupA, of unknown function, and CopA, a copper effluxing P1B-type ATPase. We show that CupA is a novel cell membrane-anchored Cu(I) chaperone for CopA, and that a Cu(I)-binding competent, membrane-localized CupA, like CopA, is obligatory for copper resistance. Bacteria were grown statically in Brain Heart Infusion media (Bacto BHI, Becton Dickinson) at 37C in an atmosphere of 5% CO2 to a culture density of OD620~0.2 and were processed as described in the related Sample record. Strain IU1781 (D39 rpsL1) served as the reference for the strain comparison. The experiment was repeated one time, and results are consistent with those observed by Shafeeq et al (Mol Microbiol. 2011). Data normalization was performed using the BioArray Software Environment (BASE 1.2; Saal et al, Genome Biol. 2002) using the Lowess (subgrid) method. Median spot intensities were normalized without background subtraction and used to calculate expression ratios. The cut-off for statistical significance of differential expression was set at an average up or down fold change of at least 1.8 fold.

ORGANISM(S): Streptococcus pneumoniae

SUBMITTER: Krystyna Kazmierczak

PROVIDER: E-GEOD-39176 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A new structural paradigm in copper resistance in Streptococcus pneumoniae.

Fu Yue Y Tsui Ho-Ching Tiffany HC Bruce Kevin E KE Sham Lok-To LT Higgins Khadine A KA Lisher John P JP Kazmierczak Krystyna M KM Maroney Michael J MJ Dann Charles E CE Winkler Malcolm E ME Giedroc David P DP

Nature chemical biology 20130127 3

Copper resistance has emerged as an important virulence determinant of microbial pathogens. In Streptococcus pneumoniae, copper resistance is mediated by the copper-responsive repressor CopY, CupA and the copper-effluxing P(1B)-type ATPase CopA. We show here that CupA is a previously uncharacterized cell membrane-anchored Cu(I) chaperone and that a Cu(I) binding-competent, membrane-localized CupA is obligatory for copper resistance. The crystal structures of the soluble domain of CupA and the N- ...[more]

PMID: 23354287

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A new structural paradigm in copper resistance in a human pathogen

Publications

A new structural paradigm in copper resistance in Streptococcus pneumoniae.

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