The copper-responsive ScsC protein of Salmonella promotes intramacrophage survival and interacts with the arginine sensor ArtI.

Abstract

The scsABCD (suppressor of copper sensitivity) locus of Salmonella encodes four proteins that resemble the disulfide folding machinery of other bacteria. Previous work has shown that Salmonella encounters toxic levels of copper during infection and the Scs system provides protection against this copper-mediated toxicity. The current work reports that expression of the soluble periplasmic protein StScsC is induced by copper and that intramacrophage survival in the presence of copper is diminished by the loss of StScsC. Using a combination of genetic and proteomic approaches, the abundance of various cysteine-containing periplasmic proteins was found to be elevated by StScsC in the Salmonella periplasm, implicating StScsC in the disulfide folding of superoxide dismutases and proteins involved in amino acid sensing and import. Co-purification and mass spectrometry approaches confirmed that the arginine-sensing periplasmic protein ArtI associates with StScsC via a disulfide interaction, and purified ArtI was shown to alter the thiol redox state of purified StScsC. This work reports the first demonstration of a redox partner for the Scs system of Salmonella and provides insights into how this bacterial pathogen responds to copper stress during infection.

• Authors: Buke Yucel, Gary K Robinson, Mark Shepherd
• Journal: The FEBS journal (FEBS J) Vol. 287 Issue 17 Pg. 3827-3840 (09 2020) ISSN: 1742-4658 [Electronic] England
• PMID: 32153092 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Federation of European Biochemical Societies.

Chemical References

• ATP-Binding Cassette Transporters
• ArtI protein, Salmonella typhimurium
• Bacterial Proteins
• Disulfides
• Periplasmic Proteins
• Recombinant Proteins
• Arginine
• Copper Sulfate

Topics

• ATP-Binding Cassette Transporters (chemistry, genetics, physiology)
• Amino Acid Sequence
• Animals
• Arginine (metabolism)
• Bacterial Load
• Bacterial Proteins (chemistry, genetics, physiology)
• Biological Transport
• Copper Sulfate (pharmacology)
• Disulfides (metabolism)
• Escherichia coli (metabolism)
• Genes, Bacterial
• Gram-Negative Bacteria (genetics)
• Macrophages (microbiology)
• Mice
• Models, Molecular
• Oxidation-Reduction
• Periplasmic Proteins (chemistry, genetics, physiology)
• Protein Conformation
• Protein Folding
• Protein Interaction Mapping
• RAW 264.7 Cells
• Recombinant Proteins (metabolism)
• Salmonella Infections, Animal (microbiology)
• Salmonella typhimurium (drug effects, genetics, physiology)
• Sequence Alignment
• Sequence Homology, Amino Acid