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The combined actions of the copper‐responsive repressor CsoR and copper‐metallochaperone CopZ modulate CopA‐mediated copper efflux in the intracellular pathogen Listeria monocytogenes
Author(s) -
Corbett David,
Schuler Stephanie,
Glenn Sarah,
Andrew Peter W.,
Cavet Jennifer S.,
Roberts Ian S.
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2011.07705.x
Subject(s) - operon , biology , repressor , copper , mutant , transcription (linguistics) , atpase , transcription factor , biochemistry , enzyme , gene , chemistry , linguistics , philosophy , organic chemistry
Summary 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 P 1 ‐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 32 bp 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 Cys 42 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.