The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae

Sulman Shafeeq, Hasan Yesilkaya, Tomas G. Kloosterman, Geetha Narayanan, Michal Wandel, Peter W. Andrew, Oscar P. Kuipers, Julie A. Morrissey*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)1255-1270
Number of pages16
JournalMolecular Microbiology
Volume81
Issue number5
DOIs
Publication statusPublished - Sep-2011

Keywords

  • MYCOBACTERIUM-TUBERCULOSIS
  • TRANSCRIPTIONAL REGULATOR
  • PSEUDOMONAS-AERUGINOSA
  • COMPETENCE PHEROMONE
  • ENTEROCOCCUS-HIRAE
  • BACILLUS-SUBTILIS
  • ESCHERICHIA-COLI
  • ABC TRANSPORTER
  • GENE-EXPRESSION
  • TRANSFORMATION

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