Molecular Analysis of the Copper-Transporting Efflux System CusCFBA of Escherichia coli
Open accessAbstract
The cus determinant of Escherichia coli encodes the CusCFBA proteins that mediate resistance to copper and silver by cation efflux. CusA and CusB were essential for copper resistance, and CusC and CusF were required for full resistance. Replacements of methionine residues 573, 623, and 672 with isoleucine in CusA resulted in loss of copper resistance, demonstrating their functional importance. Substitutions for several other methionine residues of this protein did not have any effect. The small 10-kDa protein CusF (previously YlcC) was shown to be a periplasmic protein. CusF bound one copper per polypeptide. The pink CusF copper protein complex exhibited an absorption maximum at around 510 nm. Methionine residues of CusF were involved in copper binding as shown by site-directed mutagenesis. CusF interacted with CusB and CusC polypeptides in a yeast two-hybrid assay. In contrast to other well-studied CBA-type heavy metal efflux systems, Cus was shown to be a tetrapartite resistance system that involves the novel periplasmic copper-binding protein CusF. These data provide additional evidence for the hypothesis that Cu(I) is directly transported from the periplasm across the outer membrane by the Cus complex.
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Other mechanisms for preventing Cu toxicity include Cu binding to cysteine-rich metallothioneins, such as MymT in Mycobacteriaceae and CusF in E. coli.
“Other mechanisms for preventing Cu toxicity includes Cu binding to cysteine- rich metallothioneins , such as MymT in Mycobacteriaceae 161 and CusF in E. coli 162 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [162]
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- Authors
- Franke, S., Grass, G., Rensing, C., & Nies, D. H.
- Affiliations
- Martin Luther University Halle-Wittenberg (DE)
- University of Arizona (US)
- Corresponding author
- Nies, Dietrich H.
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2003-07
- Volume
- 185
- Issue
- 13
- Pages
- 3804-3812
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC161567
- OpenAlex
- W2145307718
- Cited by
- 538
- References
- 3
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 22 · 2023: 28 · 2022: 31 · 2021: 32 · 2020: 33 · 2019: 24 · 2018: 21 · 2017: 22 · 2016: 28 · 2015: 22 · 2014: 31 · 2013: 25 · 2012: 31
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- Deutsche Forschungsgemeinschaft
- National Institute of Environmental Health Sciences (ES 04940, P42ES004940)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- copper resistance, silver resistance, CUSA, methionine residues, copper transport, Escherichia coli, heavy metal efflux, protein-protein interaction
- MeSH terms
- Biological Transport, Carrier Proteins, Copper, Escherichia coli, Microbial Sensitivity Tests, Operon, Gene Expression Regulation, Bacterial, Mutagenesis, Site-Directed, Gene Deletion, Drug Resistance, Bacterial, Escherichia coli Proteins, Periplasmic Proteins
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