We have characterized the csoR-copA-copZ copper resistance operon of the important human intracellular pathogen Listeria monocytogenes. Transcription of the operon is specifically induced by copper, and mutants lacking the P1-type ATPase CopA have reduced copper tolerance and over-accumulate copper relative to wild type. The copper-responsive repressor CsoR autoregulates transcription by binding to a single 32bp site spanning the -10 and -35 elements of the promoter. Copper co-ordination by CsoR derepresses transcription of the operon and alters CsoR:DNA complex assembly as determined by DNase I footprinting and electrophoretic mobility shift assays, with some DNA-binding capacity being retained in the presence of 2 mole equivalents of copper. Analysis of the CsoR copper sensory site demonstrated that substitution of Cys42 with Ala generated a CsoR variant that was unresponsive to copper. Importantly, in the absence of CopZ, copper responsiveness of csoR-copA-copZ expression is substantially increased, implying that CopZ reduces the access of CsoR to copper. Furthermore, CopZ is shown to confer copper resistance in mutants lacking copper-inducible csoR-copA-copZ expression, thus providing protection from the deleterious effects of copper within the cytoplasm. © 2011 Blackwell Publishing Ltd.
CITATION STYLE
Corbett, D., Schuler, S., Glenn, S., Andrew, P. W., Cavet, J. S., & Roberts, I. S. (2011). The combined actions of the copper-responsive repressor CsoR and copper-metallochaperone CopZ modulate CopA-mediated copper efflux in the intracellular pathogen listeria monocytogenes. Molecular Microbiology, 81(2), 457–472. https://doi.org/10.1111/j.1365-2958.2011.07705.x
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