A Copper-Responsive Two-Component System Governs Lipoprotein Remodeling in Listeria monocytogenes.

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Bacterial lipoproteins are crucial membrane components whose acylation affects immune recognition by Toll-like receptor 2 (TLR2).
• Listeria monocytogenes can alter its lipoprotein structure in response to environmental copper, modulating TLR2 ligand activity.

Purpose of the Study:

• To identify the regulatory mechanism controlling copper-induced lipoprotein modification in Listeria monocytogenes.
• To elucidate the role of the response regulator CopR in integrating copper sensing with lipoprotein biosynthesis and resistance.

Main Methods:

• Identification of transcription factor (CopR) using genetic and biochemical approaches.
• Analysis of gene expression via transcript analysis.
• Characterization of DNA-binding motifs for CopR.

Main Results:

• The response regulator CopR directly controls lipoprotein remodeling and copper resistance gene expression.
• Phosphorylated CopR binds to specific promoter regions, activating transcription of Lit2, Lgt2, and copper resistance determinants.
• CopR-mediated regulation is essential for copper-induced lipoprotein conversion and reduced TLR2 stimulation.

Conclusions:

• CopR acts as a key transcription factor integrating copper stress with adaptive responses in L. monocytogenes.
• Copper-induced lipoprotein remodeling by CopR reduces immune system activation, potentially aiding pathogen survival.
• This regulatory circuit may be conserved in other bacteria carrying similar copper resistance elements.