Journal article
Role of copper efflux in pneumococcal pathogenesis and resistance to macrophage-mediated immune clearance
Infection and immunity, Vol.83(4), pp.1684-1694
04/01/2015
DOI: 10.1128/IAI.03015-14
PMCID: PMC4363445
PMID: 25667262
Abstract
In bacteria, the intracellular levels of metals are mediated by tightly controlled acquisition and efflux systems. This is particularly true of copper, a trace element that is universally toxic in excess. During infection, the toxic properties of copper are exploited by the mammalian host to facilitate bacterial clearance. To better understand the role of copper during infection, we characterized the contribution of the cop operon to copper homeostasis and virulence in Streptococcus pneumoniae. Deletion of either the exporter, encoded by copA, or the chaperone, encoded by cupA, led to hypersensitivity to copper stress. We further demonstrated that loss of the copper exporter encoded by copA led to decreased virulence in pulmonary, intraperitoneal, and intravenous models of infection. Deletion of copA resulted in enhanced macrophage-mediated bacterial clearance in vitro. The attenuation phenotype of the copA mutant in the lung was found to be dependent on pulmonary macrophages, underscoring the importance of copper efflux in evading immune defenses. Overall, these data provide insight into the role of the cop operon in pneumococcal pathogenesis.
Details
- Title: Subtitle
- Role of copper efflux in pneumococcal pathogenesis and resistance to macrophage-mediated immune clearance
- Creators
- Michael D L Johnson - St. Jude Children's Research HospitalThomas E Kehl-Fie - University of Illinois Urbana-ChampaignRoger Klein - St. Jude Children's Research HospitalJacqueline Kelly - St. Jude Children's Research HospitalCorinna Burnham - St. Jude Children's Research HospitalBeth Mann - St. Jude Children's Research HospitalJason W Rosch - St. Jude Children's Research Hospital
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.83(4), pp.1684-1694
- DOI
- 10.1128/IAI.03015-14
- PMID
- 25667262
- PMCID
- PMC4363445
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Grant note
- R25 CA023944 / NCI NIH HHS 5R25CA23944 / NCI NIH HHS R01AI110618 / NIAID NIH HHS T32 HL094296 / NHLBI NIH HHS R01 AI110618 / NIAID NIH HHS K22AI104805-01 / NIAID NIH HHS K22 AI104805 / NIAID NIH HHS
- Language
- English
- Date published
- 04/01/2015
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618633202771
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