The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae
Open accessAbstract
Summary: High levels of copper are toxic and therefore bacteria must limit free intracellular levels to prevent cellular damage. In this study, we show that a number of pneumococcal genes are differentially regulated by copper, including an operon encoding a CopY regulator, a protein of unknown function (CupA) and a P1‐type ATPase, CopA, which is conserved in all sequenced Streptococcus pneumoniae strains. Transcriptional analysis demonstrated that the cop operon is induced by copper in vitro, repressed by the addition of zinc and is autoregulated by the copper‐responsive CopY repressor protein. We also demonstrate that the CopA ATPase is a major pneumococcal copper resistance mechanism and provide the first evidence that the CupA protein plays a role in copper resistance. Our results also show that copper homeostasis is important for pneumococcal virulence as the expression of the cop operon is induced in the lungs and nasopharynx of intranasally infected mice, and a copA‐ mutant strain, which had decreased growth in high levels of copper in vitro, showed reduced virulence in a mouse model of pneumococcal pneumonia. Furthermore, using the copA‐ mutant we observed for the first time in any bacteria that copper homeostasis also appears to be required for survival in the nasopharynx.
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Deletion of copA in S. pneumoniae causes reduced virulence in a mouse pneumonia model.
“Deletion of copA in S. pneumoniae causes reduced virulence in a mouse pneumonia model [216].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [216]
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- Authors
- Shafeeq, S., Yesilkaya, H., Kloosterman, T. G., Narayanan, G., Wandel, M., Andrew, P. W., Kuipers, O. P., & Morrissey, J. A.
- Affiliations
- University of Leicester (GB)
- University of Groningen (NL)
- Corresponding author
- Morrissey, Julie A.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2011-07-19
- Volume
- 81
- Issue
- 5
- Pages
- 1255-1270
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2119612735
- Cited by
- 157
- References
- 59
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 10 · 2020: 11 · 2019: 6 · 2018: 3 · 2017: 15 · 2016: 9 · 2015: 26 · 2014: 9 · 2013: 8 · 2012: 18
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (076573, 078763/Z/05/Z)
- European Commission (222983)
- Rijksuniversiteit Groningen
- Universitair Medisch Centrum Groningen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- copper homeostasis, Streptococcus pneumoniae, copper resistance, zinc regulation, transcriptional regulation, bacterial virulence, pneumococcal pneumonia, mouse model
- MeSH terms
- Copper-Transporting ATPases, Adenosine Triphosphatases, Animals, Bacterial Proteins, Copper, Homeostasis, Lung, Nasopharynx, Pneumonia, Pneumococcal, Promoter Regions, Genetic, Repressor Proteins, Streptococcus pneumoniae, Zinc, Gene Expression Regulation, Bacterial, Oligonucleotide Array Sequence Analysis, Cation Transport Proteins, Mice
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