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Updated: Feb 27, 2026
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High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
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Host and Pathogen Copper-Transporting P-Type ATPases Function Antagonistically during Salmonella Infection
Erik Ladomersky1,2, Aslam Khan1,2, Vinit Shanbhag1,2
1Department of Biochemistry, University of Missouri, Columbia, Missouri, USA.
Infection and Immunity
|June 28, 2017
Summary
Host copper transporter ATP7A is crucial for macrophage defense against Salmonella Typhimurium infection. Bacterial copper export mechanisms counteract this host defense, highlighting opposing roles in infection.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
- Trace Element Metabolism
Background:
- Copper is an essential trace element for all aerobic organisms, but it can be toxic at higher concentrations.
- The copper-transporting P-type ATPase ATP7A is vital for maintaining copper homeostasis in mammalian cells.
- ATP7A facilitates copper transport into the secretory pathway and across the plasma membrane, and is implicated in antimicrobial activity.
Purpose of the Study:
- To investigate the role of ATP7A-dependent copper transport in host defense against bacterial infection, specifically Salmonella Typhimurium.
- To determine the impact of deleting ATP7A in myeloid cells on macrophage function and susceptibility to infection.
- To explore the interplay between host copper transport and bacterial copper export mechanisms during infection.
Main Methods:
- Generation of Atp7aLysMcre mice with specific deletion of the Atp7a gene in myeloid lineage cells, including macrophages.
- Isolation and functional analysis of primary macrophages from knockout and wild-type mice.
- Assessment of bacterial killing capacity, copper transport into phagosomes, and susceptibility to systemic infection.
- Genetic manipulation of Salmonella Typhimurium to delete copper exporter genes (CopA and GolT).
Main Results:
- Macrophages from Atp7aLysMcre mice showed reduced copper transport into phagosomes and impaired killing of Salmonella Typhimurium.
- Atp7aLysMcre mice exhibited increased susceptibility to systemic S. Typhimurium infection compared to wild-type controls.
- Deletion of bacterial copper exporters CopA and GolT reduced infection severity in wild-type mice but not in Atp7aLysMcre mice.
Conclusions:
- ATP7A-mediated copper transport into phagosomes is essential for host defense against Salmonella Typhimurium.
- Bacterial copper export systems (CopA and GolT) counteract host defense by exporting copper from the bacteria.
- This study reveals opposing roles for host and pathogen copper transporters in the context of bacterial infection.
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