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Updated: Oct 6, 2025

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Regulation of DNA-binding activity of the Staphylococcus aureus catabolite control protein A by copper (II)-mediated
Xiangwen Liao1, Huinan Li2, Yu Guo3
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China; School of Pharmacy, Jiangxi Science &Technology Normal University, Nanchang, China.
Abstract:
Catabolite control protein A (CcpA) of the human pathogen Staphylococcus aureus is an essential DNA regulator for carbon catabolite repression and virulence, which facilitates bacterial survival and adaptation to a changing environment. Here, we report that copper (II) signaling mediates the DNA-binding capability of CcpA in vitro and in vivo. Copper (II) catalyzes the oxidation of two cysteine residues (Cys216 and Cys242) in CcpA to form intermolecular disulfide bonds between two CcpA dimers, which results in the formation and dissociation of a CcpA tetramer of CcpA from its cognate DNA promoter. We further demonstrate that the two cysteine residues on CcpA are important for S. aureus to resist host innate immunity, indicating that S. aureus CcpA senses the redox-active copper (II) ions as a natural signal to cope with environmental stress. Together, these findings reveal a novel regulatory mechanism for CcpA activity through copper (II)-mediated oxidation.
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