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Multiple signaling systems target a core set of transition metal homeostasis genes using similar binding motifs
Author(s) -
Garber Megan E.,
Rajeev Lara,
Kazakov Alexey E.,
Trinh Jessica,
Masuno Duy,
Thompson Mitchell G.,
Kaplan Nurgul,
Luk Joyce,
Novichkov Pavel S.,
Mukhopadhyay Aindrila
Publication year - 2018
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/mmi.13909
Subject(s) - biology , gene , operon , pseudomonas stutzeri , genetics , efflux , regulation of gene expression , microbiology and biotechnology , bacteria , escherichia coli
Summary Bacterial response to metals can require complex regulation. We report an overlapping regulation for copper and zinc resistance genes in the denitrifying bacterium, Pseudomonas stutzeri RCH2, by three two‐component regulatory proteins CopR1, CopR2 and CzcR. We conducted genome‐wide evaluations to identify gene targets of two paralogous regulators, CopR1 and CopR2, annotated for copper signaling, and compared the results with the gene targets for CzcR, implicated in zinc signaling. We discovered that the CopRs and CzcR have largely common targets, and crossregulate a core set of P. stutzeri copper and zinc responsive genes. We established that this crossregulation is enabled by a conserved binding motif in the upstream regulatory regions of the target genes. The crossregulation is physiologically relevant as these regulators synergistically and antagonistically target multicopper oxidases, metal efflux and sequestration systems. CopR1 and CopR2 upregulate two cop operons encoding copper tolerance genes, while all three regulators downregulate a putative copper chaperone, Psest_1595. CzcR also upregulated the oprD gene and the CzcIABC Zn 2+ efflux system, while CopR1 and CopR2 downregulated these genes. Our study suggests that crossregulation of copper and zinc homeostasis can be advantageous, and in P. stutzeri this is enabled by shared binding motifs for multiple response regulators.